human physiology 502 winter 13 lectures 1 and 2 handout

7/30/2019 Human Physiology 502 Winter 13 Lectures 1 and 2 Handout

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PHYSIOLOGY

502Please turn off or silence your

cell phones!


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Important Information Lecture Meeting Time: M-W-F from 1:30-3:00 PM

YES, we do start AT 1:30 SHARP, and should get out at 2:50!

Course Director

Beth Rust, Ph.D.

[email protected]

615-3173

Textbook- Vanders Human Physiology, 12th edition, 2010 withCONNECT. Authors are Widmaier, Raff and Strang, McGraw Hill.

2012 Lecture Figures- Files of slides presented in Lecture will be availableon the web site.

Web Site: ctools.umich.edu/portal. Login. Click on the Physiol 502 tab atthe top of the screen or in the pull down menu on the right.


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CTOOLS Website CTools access is required.

Assignments will be posted on CTools All Resources and Course Information and Announcements will be

posted on CTools.

Scores will be posted in the Gradebook on CTools

You must check CTools regularly. Once material is posted

there, you are responsible for knowing it. Forums will be monitored by me.

Material questions can be posted there and I will answer.

All students can therefore benefit from the questions/answers

Chat Room is for student-communication regarding thecourse material. I will NOT be checking the accuracy of information posted in the

Chat Room.

If you are looking for a study group or other student communicationsregarding 502, please use the Chat Room.


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McGraw Hill CONNECT

Registration instructions have been posted onCtools in Resources.

I will use this as an online RESOURCE There will NOT be quizzes, tests or assessmentsthat are required for your grade posted onCONNECT.

There WILL be quizzes and other resourcesutilized that will be useful study tools posted onCONNECT.


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Important Information

Lecture Schedule- see Syllabus

Office hours

By appointment with me throughout the semester

By appointment with the professor who is teaching at the

time Exams

Policies and dates are listed in the syllabus

A Make-Up Exam is available but only for excused

absences. Your absence must be for unusual

circumstances, sudden illness or prolonged illness and

must be approved by Dr. Rust. In most cases,

documentation/proof of excuse is necessary

Exam dates are also listed within the lecture schedule.


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Tutorial and Written Assignments

Online Tutorial and Quiz Tutorial slides/notes file is available in Resources

Quiz is in Ctools Test Center

Tutorial Quiz is available through Friday, January 18 at

11:59 PM. Required

Written Assignment

Will be integrated case that require some outside

research/reading along with applying knowledge from class

Can work together but submitted document must be your

individual work.

More information when the assignment is posted.


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Evaluations

We utilize the medical schools evaluationsystem, not CTools.

The Unit faculty evaluations will be availableimmediately after each unit for the professors

who have most recently taught. 0.25 point extra credit is awarded for each facultyevaluation you complete

The course evaluation at the end of the term isworth 0.5 point extra credit.

Reminders to complete the evals are sent toEVERYONE EVERYTIME. If youve filled out the unit or course evals, then just

ignore the reminders.


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Pay attention to the information

provided: It is your responsibility to be aware of the

policies and information provided (1) in

the syllabus, (2) on the website and (3) inannouncement slides

If you email me a question about

something provided in the slides, thesyllabus or on the website, my response

will be for you to check your resources.


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IMPORTANT QUESTIONS:

1. Do you NEED to sleep?

2. Why or Why not?


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IMPORTANT QUESTIONS:

1. Will lack of sleep really affect

a. my attention and alertness,

b. my learning,c. whether I get sick and

d. how fast I get well

????????????????????????????????


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YES!


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What is Sleep?

Sleep is a reversible behavioral state of

perceptual disengagement from, and

unresponsiveness to the surroundingenvironment.

Sleep is regulated by circadian rhythms

and by homeostatic mechanisms.


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Electroencephalogram (EEG) patterns during

the AWAKE state compared to the different

stages of SLEEP.

Stages of sleep are characterized by differences in

the frequency and amplitude of EEG waves.

Stage 1 comprises light sleep with low-amplitude

waveforms.

Stage 2 is characterized by sleep spindles (the

higher frequency waves) and K-complexes.

Stages 3 and 4 comprise slow-wave sleep (SWS)

with high-amplitude waves and a deeper level of

unconsciousness.

The above four stages comprise non

rapid eyemovement (NREM) sleep.

The final stage is rapid eye movement (REM) sleep,

which is associated with q-activity (all waves

shown) and, in some individuals, with low-

amplitude sawtooth waves (not shown) and a higher

level of consciousness. [From Carlson, N. R.

(1994).Physiology of behavior. Boston: Allyn and

Bacon.]

How do we

determine sleep?


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14 2001 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

Sleeping brain, learning brain. The role of sleep for memory systems.

Peigneux, Philippe; 1, CA; Laureys, Steven; Delbeuck, Xavier; Maquet, Pierre

Neuroreport. 12(18):A111-A124, December 21, 2001.

Distribution of Sleep Stages during a nights sleep

1. Sleep is cyclical: Progression= Awake NREM

(some or all of Stage 1234 back up to

1), then into REM.

2. SWS (3 and 4) predominate in first half of night.

REM predominates in the second half of the

night: may not go through all NREM stages.3. Each full sleep cycle through NREM and REM

takes 90-100 minutes typically.

Sleeper does not

enter stage 4 at all


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Does lack of sleep affect alertness

and attentiveness? 24 hours of continuous wakefulness (ie. in 1st year

medical residents) impairs cognitive performancecomparable to having a blood alcohol level of 100mg/dL(legal intoxication).1

Extended work shift doubles the risk of motor vehiclecrash compared to non-extended shift for first yearresidents.2

On laparoscopic surgery simulator tasks, trainees haddouble the errors after a 17 hour night work shift without

sleep compared to performance after a night withadequate sleep.3

Significant increase in accidental needle sticks and cutswith sharp instruments for residents after extendedduration work shifts (24 hours on call).4

References: 1Dawson et al. Fatigue, alcohol and performance impairment. Nature. 1997; 388:235. 2Barger et al. Extended work shifts and the risk of motorvehicle crashes among interns. N Engl J Med. 2005; 353:125-134. 3Grantcharov et al. Laparoscopic performance after one night on call in a surgical

department; prospective study. BMJ. 2001; 323: 1222-1223. 4Ayas et al. Extended Work Duration and the risk of self-reported percutaneous injuries in

interns.JAMA. 2006; 296: 1055-1062,


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Sleep and Learning

Studies have shown that post-training sleep isimportant for learning and memory consolidation

(transfer of memory from short term to long term

memory)

Sleep deprivation can decrease learning and

memory

Sleep after learning can increase performance

Different types of learning may require different

phases of sleep.


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If you wont sleep all night, at least take

a NAP!

60 or 90 minute nap including SWS and REM, increased

same-day performance on visual perception task.

Mednick, Nakayama and Stickgold,

Nature Neuroscience 6(7):697-8, 2003


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Nap with REM as good as a night

Mednick, Nakayama and Stickgold,Nature Neuroscience 6(7):697-8,

2003

+ 1 nights

sleep+ 1 nights

sleep (no nap, testedon day 3)

Dashed line shows Nap w/REM groups

improvement on Day 1...note that it is equivalentto the improvement with a full nights sleep!

(no nap,

tested only

on day 2)


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Additional Notes

REM sleep may not be required for alltypes of learning.

Can see improvement in procedural

(virtual maze navigation) and declarativememory (people, places, things) with napcontaining SWS without REM.

For learning and memory: Bottom line-if you cant or wont sleep an entirenight, at least take about a 90 minutenap!


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Another thing about sleep

It helps our immune system fight infection.

You will be exposed to viruses during this

school year (colds, H1N1, H3N2, Influenza B). Protect yourself with sleep.

If sick, sleepiness is a part of the immuneresponseso sleep more and allow your

immune system to do its job!

Sleep deprivation decreases our ability to fightinfection.


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The Immune System

White Blood Cells (WBCs) derived from precursor cells in the bone

marrow

phagocytes (granulocytes, monocytes / macrophages)

lymphocytes (B and T cells), and natural killer (NK) cells

These cell types release chemical messengerscalled cytokines- that coordinate the immune

response- and may alter (typically increase)

sleep during infection.


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Simplified principles of

immunity

An immune response is triggered by

interaction white blood with foreign proteins

on bacteria or virus (antigens)

Interaction causes release of cytokines,

proliferation/differentiation of white blood

cells and production of antibodies

Memory cells are also produced that increase

the ability to remove/destroy the virus or

bacteria upon future exposure.22


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Effect of sleep deprivation on response to immunization.Spiegel, K., Sheridan, J.F., Van Cauter, E. JAMA 288:1471-1472, 2002

Purpose: To examine the effects of sleep deprivation on immuneresponses to influenza vaccination

Methods: Twenty five male adults (mean age 23), monitored in alaboratory. One group (n=11) had sleep restricted to 4-h / night for four(4) nights. The other group (n = 14) served as controls. All subjectswere immunized against influenza, and a blood sample taken 10 dayslater.


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Effect of sleep deprivation on response to immunization.Spiegel, K., Sheridan, J.F., Van Cauter, E. JAMA 288:1471-1472, 2002

Results: Mean antibody titers of subjects vaccinated during sleep debtwere 50% less than those of controls.

Conclusions: Responses to vaccination may be impaired in individualswith chronic partial sleep restriction. Adequate amounts of sleep areneeded for optimal resistance to infectious challenge.


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Purpose: To assess the influence of sleep on adaptive immune function

in humans.

Methods: Nineteen healthy adult subjects not previously infected with

hepatitis A were studied in a sleep laboratory. Subjects were allowed

normal sleep (n = 10) or were kept awake (n = 9) throughout the night.

They were vaccinated with inactivated hepatitis A. Blood samples were

taken for 28 days.


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Results: Hepatitis A virus antibody titers at the end of the study in thegroup allowed regular nocturnal sleep were 97% higher than in the sleep

deprived group.

Conclusions: Data suggest that sleep improves the formation of antigen-

specific immune defense as reflected by antibody production in humans.

Results underscore the importance of sleep for immunocompetence.


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The POINT isSleep is important for

1. ALERTNESS and FOCUS

2. LEARNING and MEMORY

3. THE ABILITY TO FIGHT INFECTION

Sokeep this in mind as youre deciding whether totake a nap/go to bed ? or reach for anotherenergy drink ?hmmmwhich should youdo?...the better choice for your performancein school AND your health is to get some

sleep!

L t 1 d 2


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Lectures 1 and 2

1. Homeostasis

11th: Chapter 1, pages 2-12

12th: Chapter 1, pages 2 - 12

2. Cell Structure/Membranes11th: Chapter 4, pages 97-102; Chapter 6 pages

144-157

12th: 96100, Chapter 6 pages 142-155

3. Synaptic transmission and signal integration

11th: Chapter 6, pages 138-143 and 159-171

12th: Chapter 6, pages 136141 and 156-168


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QUESTIONS to be ANSWERED

in PHYSIOLOGY 502

What does it do? FUNCTION

How does it do it? MECHANISM

How is it controlled? REGULATION


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Figure 1-1

Levels of Cellular

Organization


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Internal Environment = extracellular fluid (ECF) = plasma + interstitial fluid


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Fig. 1-2- Fluid Compartments


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HOMEOSTASIS

The maintenance of a relatively stable

internal environment

The internal environment is the extracellularfluid: interstitial fluid + plasma


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Homeostatic Control Systems

Systems which perform compensatoryregulatory responses

Involve REFLEXES = stimulus-response sequences

Involve NEGATIVE FEEDBACK: response causes

return of variable toward original set point

Examples of variables regulated include

Body Temperature

Plasma concentrations of Na+, K+, Ca2+, H+

Blood Pressure

Plasma oxygen and carbon dioxide

F db k


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Feedback

STIMULUS RESPONSEfeedback

NEGATIVE FEEDBACK: - major mechanism maintaining homeostasis

Response moves stimulus in a direction opposite to (negative to) thedirection of the original stimulus (or the original change).

POSITIVE FEEDBACK: - unstable - explosive

Response moves stimulus in the same (positive) direction

as the original stimulus.

Examples: blood clotting

parturition

LH surge during ovarian cycle

pepsin activation in stomachrising phase of action potential

reflex arc

H t ti

C t l S t


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Integrating Center

Afferent

Pathway

Efferent

Pathway

Receptor Effector

STIMULUS RESPONSE

CONTROL SYSTEM

nerves and

hormones

nerves and/or

hormones

muscle &

glands

Negative Feedback

Homeostatic Control SystemHomeostatic Reflex Arc


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Input = heat production via

metabolismOutput = heat loss to external

environment

Variable = body temperature

When input = output, defined as Steady State:

a system in which a variable is not changing, but

energy must be continuously added to maintain the

variable in constant state.

Example: body temperature


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stimulus - detectable change in external or internal environment

receptor - detects the environmental change

Fi 1 6 H t ti fl i t T t h


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Fig. 01.06

Figure 1-6: Homeostatic reflex in response to Temperature change


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Normal T ranges from 36-38oC (97-100.5oF).

Homeostatic mechanisms maintain T within this range around the set point

when faced with various challenges (exercise, external T changes, etc)

New steady state T is

slightly less than

original T.

Difference between =

error signal.

Figure 1-9


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Figure 1.09

Figure 1 9

1. Variables are not

constant, butfluctuate around

a set point.

2. Variables and/orset points also

fluctuate over a

24 hour period=

circadian rhythm


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Exam Type Question:1. Which of the following describes a homeostatic

reflex arc?a. An increase in blood K+ levels stimulates the release of

aldosterone, which promotes renal excretion of K+ anda reduction of blood K+ levels.

b. Activation of parasympathetic neurons increases insulinsecretion whereas activation of sympathetic neuronsdecreases insulin secretion.

c. During childbirth, oxytocin secretion causes contractionof uterine smooth muscle, which causes the baby to

push against the cervix, which increases oxytocinsecretion, which increases contraction of the uterinesmooth muscle.

d. Increasing diameter of axons increases the speed ofpropagation of an action potential

e. Both a and c

I t ll l C i ti i i d


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Intercellular Communication is required

Start here 9/10

Fi 1 7


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Fig. 01.07

Figure 1-7

Types of

ChemicalMessengers


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ProblemUse the following components to draw/describe the

homeostatic reflex arc response to an increase inbody temperature. A component may be used once,more than once, or not at all. Be sure to mentionwhat type of feedback is occurring.

1. smooth muscle of the blood vessels (dilates toincrease skin blood flow)

2. Brain and spinal cord

3. Temperature sensitive nerve endings

4. Nerves and hormones

5. Sweat glands (increase sweat production)

6. body temperature


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What should you have learned?

Importance of Sleep

Definition of internal environment, homeostasis

Components of a homeostatic control systemReflex arc, feedback, error signal

Types of feedback

Methods of cellular communication.


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Membrane Potential

47


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Typical Cell at Rest

K+Na+

K+

Na+

Cell Membrane

Intracellular Fluid

Extracellular Fluid

K+leak

Channels

Na+leak

Channels

ATP

2 K+

3 Na+

Na+/K+ Pump

Ions are essentially lipid insoluble but can have


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Ions are essentially lipid insoluble but can have

high permeability. How?

Ion Channels- integral membrane proteins that forma water-filled pore through which ions can diffuse

Ion channels exhibit Selectivity

Size of pore and location of charged and polar surfaceswithin the pore allow only a certain ion to diffuse

Ion channels can be Gated or Non-Gated

Non-gated channels are referred to as leak channels

Gated channel opening/closing is regulated

Ligand-gated- open/close due to binding of specific molecule Voltage-gated- open/close due to changes in membrane potential

Stretch sensitive ormechanically gated- open/close due tochanges in membrane stretch or shape

There may be several different types of channels for

the same ion

Membrane Potential


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Membrane Potential

K+K+K+X-K+X-K+X-

X-K+X-K+X-K+X-

Na+

Na+

Na+

Na+

Na+Na+

Na+

Na+Cl-

Cl-Cl-Cl-

Cl-

Cl-

Cl- Cl-

Na+

Na+

Na+

Na+

Na+Na+

Na+

Na+

Cl-

Cl-

Cl-Cl-

Cl-

Cl-

Cl-

Cl-

K+X-K+X-K+X-K+X-

K+X-K+X-K+X-K+X-

X-

0- +

0

- +

Potential (V)- separation of electric charge, magnitude measured in volts.

Membrane potential is expressed as potential of the inside of cell with

respect to the outside of cell.Ohms Law: V = IR where I = current and R = resistance

Forces that move ions through channels


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Forces that move ions through channels

Figure 6-10


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Membrane is permeable to K+

Ion movement:

K+ crosses into

Compartment 1

Na+ stays in

Compartment 1

In box (e), the chambers have reached

ELECTROCHEMICAL EQUILIBRIUM for K+:

The K+ chemical gradient (concentration gradient) is equal and opposite the

electrical gradient. The membrane potential at which K+ is at electrochemicalequilibrium is called the K+ equilibrium potential (EK):

g

Membrane is permeable to Na+


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p

Ion movement:

Na+ crosses into

Compartment 2;

but K+ stays in

Compartment 2.

When the membrane potential is = Na+ equilibrium potential (ENa):

Then there is no net flux of Na+ and the chambers have reached

electrochemical equilibrium for Na+

Figure 6-11


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Every ion has an

Equilibrium Potential (Eion) For a specific ion, Eion is the membrane potential

at which the electrical driving force is equal and

opposite the concentration gradient driving forcefor that ion.

Each ion has a different equilibrium potential.

Equilibrium potential is expressed as inside

charge relative to outside.

What determines the value (magnitude) of the

equilibrium potential?


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EKand ENa

Equilibrium potential is expressed as insidepotential relative to outside.

Based on our discussion so far, is EK

negative or positive? Based on our discussion so far, is ENa

negative or positive?

K+ K+

Na+Na+


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Determining the Membrane Potential*:

The GHK Equation

Vm = 61 log PK[Ko] + PNa [Nao] + PCl [Cli]

PK[Ki] + PNa [Nai] + PCl [Clo]

The membrane potential depends on

1. the equilibrium potentials of the permeable ions2. the relative permeability of the membrane to each ion

*You will NOT have to calculate membrane potential values

P = permeability (number of OPEN ion channels)

Resting membrane potential


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Potential (mV)

0

-90

+60

K+ equilibrium potential

Na+ equilibrium potential

Na+Na+

+ +

+-

--

K

+

K+

++

+ -- -

resting membrane potential

Resting Vm

closer to EK

than to ENa

WHY?

g p


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Na/K ATPase(Na/K Pump)

Establishes theconcentration gradients

( ) C i di


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Figure

6-13

(a) Concentration gradients

established by pump

(b)Greater K+ efflux through

leak channels than Na+

influx through leakchannels, so negative

membrane potential

develops

(c) Steady state- resting

membrane potential- total

charge flux across the

membrane reaches steadystate- Vm is stable

DevelopmentOf Resting

Membrane

Potential

Na+ and K+ Concentration Gradients are


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created and maintained by theNa+/K+Pump

K+Na+

K+

Na+

Cell Membrane

Intracellular Fluid

Extracellular Fluid

+

Resting Vm = -70 mV

(inside compared to outside)

K+ Channels

(leak)

Na+ Channels

(leak)

ATP

2 K+

3 Na+

Na+/K+ Pump


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The membrane potential can change as a

result of:

1. Change in the relative permeability of membrane

to ions.

2. Change in the electrogenic pump rate.

3. Change in the ion concentration gradient for a

permeant ion.


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Neurons(Muscles and glands too)

can change their Resting MembranePotentials to produce a signal (dv)

1. Graded Potentials - signal over shortdistances

2. Action Potentials - signal over long

distances

These transient changes in Vm are

caused by changes in membrane

permeability to ions


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For a typical cell: What would happen to


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yp pp

Membrane Potential if Na+ channels were opened?

K+ channels were opened?

Na+ channels were opened first, and then K+ channelswere opened and Na+ channels were closedsimultaneously?

Na+ channels were opened briefly and then closed?

Ca2+ channels were opened? ([Ca2+] is high outside

compared to inside)


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Two additional scenarios:

If a cell has a resting Vm = -100 mV andEK= -90 mV, would opening of K

+

channels lead to net efflux, influx or no netflux of K+? Would the Vm depolarize,hyperpolarize or stay the same?

If a cell has a resting Vm = -10 mV and anENa= +30 mV, would opening of Na

+channels lead to net efflux, influx or nonett flux of Na+? Would Vm depolarize,

hyperpolarize or stay the same? 67


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What you should have learned:

Basic principles of bioelectricity

Membrane potential- how it is established,

how it is changed

Equilibrium potential, driving force

Depolarization vs. hyperpolarization

Effect of opening various ion channels on

membrane potential


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Graded Potentials

Action Potentials

Synaptic Transmission

Neurons (and other


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initial segment

Neurons (and other

excitable cells) use

transient changes in

membrane potential as asignaling mechanism

Two types of signals:

1. Graded potential

2. Action potential


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Definitions- for the context of

excitable membranes Stimulus = something that evokes a membrane

potential change

Molecule binding to a receptor (neurotransmitter,hormone, paracrine factor)

Sensory stimulus- touch, pressure, light, sound

The change in the membrane potential is caused

by the opening or closing of gated ion channels Graded potential

Action potential


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Graded Potentials

Graded potentials are changes in

membrane potential that are

confined to a small region of the cellmembrane and for which amplitude

is determined by stimulus strength.

Action potential


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A brief, large depolarization of the membrane that occurs due to

opening of V-gated channelsAll-or-None

If threshold is reached, an AP fires. If threshold is not

reached, an AP does not fire

Every action potential fired by a given normal, resting cell

looks exactly the same

Has a threshold, a refractory period and is conducted without

decrement.

Action potential

Cells which are capable of generating action potentials

Neurons, muscle cells & certain endocrine, immune and

reproductive cells

Excitable Cells


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What is THRESHOLD?

It is the depolarized membrane potential at which thespecific voltage-gated channels that generate an action

potential will open

Threshold is reached via graded potential changesto the membrane, due to opening of ligand gatedchannels (ie. neurotransmitter receptor channels) orother (different) V-gated channels (ie. pacemaker

potentials)

When the membrane has depolarized to threshold viathe flux of ions through the initially opened channels,then a specific set of V-gated channels open and anaction potential occurs

Graded


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G aded

Potentials

Graded Potential Propertiesno threshold

no refractory period

graded amplitude

graded duration

decremental conduction

can be excitatory orinhibitory

Important for signaling

over short distances

Can be summed to reach

threshold

Figure 6-15

Excitatory potential Inhibitory potential

Excitatory Post Synaptic Potential - moves Vm towards threshold


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y y p mInhibitory Post Synaptic Potential - moves Vm away from threshold


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Examples of Ion Fluxes that generate EPSPs and IPSPs

Fig. 6-17: Leakage of Charge causes decremental


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conduction = decay of signal

Longitudinal current

Transmembrane

Current

Action potentials do NOT


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Threshold

Action potentials do NOT

have decremental

conduction

Signal over

long distances


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Fig. 06.18

1. Resting Membrane Potential

Figure 6-19


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Time (ms)

1. Resting Membrane Potential

12 EPSP

Graded depolarization- example

NT binds and opens ligand-gated

Na+

channels.V-gated Na+ and K+ channels still

closed

2. EPSP reaches threshold

V-gated Na+ channels opendepolarization

3. Positive feedback.

DepolarizationMore V-gatedNa+ channels open

4. Na+ channel inactivation occurs

AND slowly opening V-gated K+

channels open

Na+ influx stops. K+ efflux

increases.

5. Rapid repolarization to Vm

Na+ channels close at -70 mV

6. Hyperpolarization (after-hyperpolarization)

K+ channels still open.

7. Return to Vm = -70 mV

V-gated Na+ and K+ channels are

both closed.

Refractory Periods


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Absolute refractory period

relative refractory period

Refractoryperiods limit

AP frequency

Na inactivationgate removed by

repolarization

Absolute: Na+ channels are inactive and CANNOT re-open

Relative: Na+

channels can open, but hyperpolarized membranerequires larger EPSP to reach threshold

Figure 6-21

Th h ld


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Fig. 06.21Threshold:Relationship between

Stimulus Strengthand Action Potential

Generation:

All action potentials

from a given normal

(resting) cell look

exactly the same (all-or-

none).

So, how is stimulus

intensity encoded?

Suprathreshold

stimuli

(Post Synaptic) Dendrites and cell bodies: receive information via

neurotransmitters then undergo graded potentials


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neurotransmitters, then undergo graded potentials.

Axons: Action potentials propagate to axon terminal to result in

release of neurotransmitters.

If enough excitatory

Graded Potentials are

produced to depolarize the

initial segment tothreshold, then Action

Potentials are fired

Nucleus

Figure 6-

22


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Fig. 06.22ab

g

Action Potential

Propagation

Figure 6-22 Action Potential Propagation


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The propagation of the action potential from the dendrite to the axon-

terminal is forwardbecause the absolute refractory period follows along in the wakeof the moving action potential. Action potentials occur instead of graded potentials because

there are many voltage gated Na channels in the membrane. Therefore, small changes incurrent flow will open many channels and threshold will be easily reached.

Local currents

Conduction Velocity (also calledP ti R t ) ff t d b


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Propagation Rate) affected by:

Diameter of axon- Larger = faster (less resistance to local currentfaster ion

flow)

Myelination- less leakage of charge (transmembrane current) where

there is myelin Local current flow can flow farther/faster down axon

(longitudinal current) to depolarize a more distant regionto threshold

Ions leak out at nodes of Ranvier.

Nodes have high density of V-gated Na+ channels: anotherAP fires

Saltatory conduction: action potentials appear to jumpfrom one node to the next as they propagate along

myelinated axon, up to 225 mi/h

Figure 8

-3c


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Peripheral NS


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Figure 06.02ab

The myelin sheath speeds up the conduction

of electrical signals along the axon

Exposed to extracellular fluid

Central NS

Velocity of propogation depends on fiber diameter and myelination


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Saltatory Conduction: Action potentials jump from one node to the

next as they propagate along a myelinated (insulated) axon.

Maximum conduction velocity = ~225 mi/hr

Low concentration of

voltage -gated Na channels

High concentration of

voltage -gated Na channels


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myelin

myelin

not myelinated

myelinated

nodes of Ranviersaltatory conduction

Conductionvelocity as low as

1 mi/h (4 seconds

for signal to go

head to toe)

Conduction

velocity as fast as225 mi/h (.02

second for signal

to go head to toe)

Wh t if bl k d th i f


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What if you blocked the opening of

V-gated K+

channels? Would AP frequency be affected? Explain.

Would conduction velocity (propagation

rate) be affected? Explain.


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Membrane potential- how it is established,how it is changed

Equilibrium potential, driving force Graded potentials and action potentials-

properties and differences

Generation and propagation of actionpotentials

Role of Myelination


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Neural Tissue, Synapses and

Signal Integration

Dendrites: receive information via neurotransmitters, then undergo

graded potentials.


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Axons: generate action potentials that propagate to terminals,

from which neurotransmitter is released onto other neurons orother cell types (ie. muscle, glands).

Cell Body: receivesinformation via

neurotransmitters, then

undergoes graded

potentials.

Nucleus

SYNAPSE: specialized junction between two neurons where one

neuron alters the electrical and chemical activity of another


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Figure 06.03

(99%)

(nerve fiber)

(no dendrites)

y

SYNAPSES

How Many Synapses?


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How Many Synapses?

In a piece of brain the size of a grain of sand:100,000 neurons

2,000,000 axons

1,000,000,000 synapses

In the CNS:

100 billion neurons

100 trillion interneuronal connections

Depolarization causes

to open

Fig. 6-27


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to open

(ligand-gated channels)Unbound

NT docking

Ca2+ binds

via SNAREs, get

fusion and NT

release


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Summary: Presynaptic neuron APPostsynaptic Potential


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Postsynaptic Potential1. AP arrival at presynaptic axon terminal opens V-gated Ca2+

channels

2. Ca2+ initiates NT release into synaptic cleft

1. Via binding to synaptotagmin and SNARE interactions

3. NT diffuses across cleft and binds to receptor on

postsynaptic cell

4. Opening of ligand-gated channel (directly gated or G-protein coupled channel) generates EPSP or IPSP inpostsynaptic cell (and may lead to changes in postsynaptic

AP firing)5. Unbound NT is removed from cleft:

1. Diffuses away

2. Is transported back into presynaptic cell or glial cells

3. Is metabolized by enzyme on post-synaptic membrane


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Ionotropic

NT binds to protein and protein changes conformation to

open the intrinsic ion channel.


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Metabotropic

NT binds to receptor, G protein

activated, G protein interacts with

channel to cause opening

NT binds to receptor, 2nd messenger

cascade occurs, 2nd messenger interacts

with channel to cause opening


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Postsynaptic Cell is influenced by

multiple Presynaptic inputs:

1. Thousands of synapses on any one

neuron

2. Hundreds activated simultaneously

3. How are these inputs combined inthe postsynaptic cell?

Many inputs to post-


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synaptic cell body

and dendrites

Output (AP

frequency) is result

of sum of total input:Total EPSPTotal IPSP

If sum of inputs is

above threshold:APs fire. Greater

excitatory inputs

greater APfrequency

Figure 6-32


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Fig. 06.32EPSPs and IPSPs

Synaptic Integration need many EPSPs to reach threshold


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Panel 1: Two distinct, non-overlapping, graded depolarizations- no

summation.

Panel 2: Two overlapping graded depolarizations demonstrate temporal

summation (more ion channels open).

Panel 3: Distinct actions of stimulating neurons A and B demonstratespatial summation.

Panel 4: A and B are stimulated enough to cause a suprathreshold

graded depolarization, so an action potential results.

Panel 5: Neuron C causes a graded hyperpolarization; A and C effects

add and they cancel each other out.


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Problem

A drug acts to decrease the frequency of

action potentials in the postsynaptic cells.

Suggest 3 possible mechanisms by whichthe drug acts.



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Basic structure of a neuron (dendrites, cell body,axon, terminals)

Synaptic transmission

Sequence of events from AP in presynaptic cell to EPSP,

IPSP and AP in postsynaptic cell Removal of neurotransmitter from the post

synaptic terminal (3 mechanisms).

The difference between ionotropic andmetabotropic neurotransmitter action

Summation and integration in postsynaptic cell

human physiology 502 winter 13 lectures 1 and 2 handout

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