1 a, b, c, d all move solutes by diffusion down concentration gradient
DESCRIPTION
3 Final mechanism can work against gradient e. Active transport XXX XX XXX XTRANSCRIPT
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a, b, c, d all move solutes by diffusion down concentration gradient
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Final mechanism can work against gradient e. Active transport
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Final mechanism can work against gradient e. Active transport
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Final mechanism can work against gradient e. Active transport
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Final mechanism can work against gradient e. Active transport
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Pump Protein
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Final mechanism can work against gradient e. Active transport
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Final mechanism can work against gradient e. Active transport
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ATP
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Final mechanism can work against gradient e. Active transport
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ATP
ADP + Pi
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Final mechanism can work against gradient e. Active transport
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Final mechanism can work against gradient e. Active transport
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Concentrates against gradient
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Ion pumps
Uniporter (one solute one way): I- pump in thyroid
Coupled transporters (two solutes) Symporter (same direction):Antiporter (opposite directions)
Na+/K+ ATPase in mitochondria
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3. Cells can control solute distribution across their membranes by controlling:a. Synthesis of integral proteinsb. Activity of integral proteinsc. E supply for pumpsTherefore, expect that solutes would be unequally distributed across membranes
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4. Actual ion distributionsSquid Axon (mM):ION [CYTOPLASM][ECF]Na+ 50 460K+ 400 10Cl- 40 540Ca++ <1 10A- 350 <1
Organic anions with multiple - chargesCOO- on proteins, sulfates, phosphates, etc....
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5. Reasons for unequal distributiona. Metabolic production of organic anions A- produced by biosynthetic machinery
inside the cellb. Membrane permeability
impermeable to A- moderate Cl- permeability30-50X more permeable to K+ than
Na+
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Given a and b, system passively comes to unequal ion distribution
Diffusion of ions governed not only by their concentration gradients, but also their electrical gradients
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Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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1 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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1 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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1 M sucrose 0.5 M sucrose
0.5 M sucrose
Permeable uncharged solutes will come to equilibrium across membranes if no other forces acting
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Permeable charged solutes will not come to concentration equilibrium across
membrane if other charged impermeable solutes are present
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Na+
A-
Impermeable
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Na+
A-
K+ Cl-
Permeable
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Na+
A-
K+ Cl-
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Na+
A-
K+ Cl-
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out is exactly balanced by the electrical force
(electromotive force) holding K+ in
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out is exactly balanced by the electrical force
(electromotive force) holding K+ in Result: an unequal ion distribution which will
be maintained passively
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Na+
A-K+
Cl-Na+
A-
K+ Cl-
At equilibrium: chemical force driving K+ out is exactly balanced by the electrical force
(electromotive force) holding K+ in Result: an unequal ion distribution which will be
maintained passively“Donnan Equilibrium”
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Donnan Equilibrium resembles situation in real cell, with one exception:cell is not maintained passively
Poison real cell and unequal distribution eventually goes away
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c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-Na+Na+/K+ ATPase
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
Na+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
Na+K+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Na+
A-
Na+
K+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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If Na+ allowed to build up, inside becomes + , drives K+ out, and lose unequal distribution
Na+
A-
Na+
K+
c. Cells work via pumps to maintain unequal ion distribution
Na+ “leaks” in down chemical and electrical gradients
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Therefore, cells use combination of active and passive mechanisms to maintain unequal ion distributions REASON?
B. Membrane Potentials1. Significance of unequal distributionsWhenever an ion is unequally distributed
across a membrane, it endows the membrane with an electrical potential“membrane potential” (EM or VM)
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2. Membrane potential measurementa. Voltmeter
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2. Membrane potential measurementa. Voltmeter
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2. Membrane potential measurementa. Voltmeter
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2. Membrane potential measurementa. Voltmeter
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2. Membrane potential measurementa. Voltmeter
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b. Calculate with Nernst equationEM = RT x ln[ion]outside
FZ ln[ion]inside
R = gas constant, T = abs. temperatureF = Faraday constant, Z = valance
Magnitude of the voltage due to 1 unequally distributed ion is directly proportional to the magnitude of its unequal distribution
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BUT: can't use it for a real cellonly valid for 1 iononly valid for freely permeable ions
Can use it to calculate voltage due to any one freely permeable ion in a mixturee.g. K+ = -91 mV
Na+ = +65 mV
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c. Alternative: GOLDMAN EQUATIONaccounts for multiple ionsaccounts for permeability of each multiplies [ion] ratios X permeability
constant for each ion, then sums up all to get total membrane EM
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d. CONCLUSION: In ion mixture, each ion contributes to the overall EM in proportion to its permeability
Most permeable ions contribute the most charge
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Which ion is most permeable? K+
real cell: inside is -80 mV = resting EM
cell is “negatively polarized”
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EM is due almost exclusively to the unequal distribution of K+
Changes in [K+] alter EM easily
Changes in [Na+] do not alter EM
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All cells have resting potential due to ion distributions
Some cells can use this electrical potential to transmit information
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C. Nervous System Components1. Glial cells: supportive
diverse functions supportinsulationprotectioncommunication
up to 90% of nervous system by weight
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2. Neuronssoma: nucleus, usual organellesdendrites: receptive, inputaxon: transmission (microm to m)axon terminals: synapse, output
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3. Integrated Function of NeuronsGenerate and conduct electrical signals for communication or coordination
a. Propagation of electrical signals along individual cells (wires)
b. Communication of electrical information between cells
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c. Model system for study: Squid giant axon (J.Z. Young)
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c. Model system for study: Squid giant axon (J.Z. Young)
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D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
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D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
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D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
recording electrode
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D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
recording electrodecoupled with stimulating electrode
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D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
recording electrodecoupled with stimulating electrode
64Can change EM by adding charge
D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
recording electrodecoupled with stimulating electrode
65Can change EM by adding charge
+++
D. Electrical Characteristics of Neurons1. Intracelluar Recording:Hodgkin and Huxley
recording electrodecoupled with stimulating electrode
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STIMULUS
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STIMULUSmV
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STIMULUS
RESPONSE OF CELL
mV
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STIMULUS
RESPONSE OF CELL
EM
(mV)
mV
0
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STIMULUS
RESPONSE OF CELL
EM
(mV)
mV
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
Add negative charge, EM gets more negative0
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EM
(mV)
mV
-80
HYPERPOLARIZATION
Add negative charge, EM gets more negative0
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EM
(mV)
mV
-80EM moves away from 0 HYPERPOLARIZATION
Add negative charge, EM gets more negative0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
Add positive charge, EM gets more positive0
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EM
(mV)
mV
-80
Add positive charge, EM gets more positive
DEPOLARIZATION
0
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EM
(mV)
mV
-80
Add positive charge, EM gets more positive
DEPOLARIZATION EM moves towards 0
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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2. Passive responsesa. Magnitude directly proportional to amount of current
Increase current: increase magnitude of passive depolarization
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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b. Magnitude inversely proportional to distance from stimulus
Die out locally
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EM
(mV)
mV
-80
0
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EM
(mV)
mV
-80
0
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3. At some point, small increase in applied current triggers a membrane depolarization much greater than the stimulus currentActive responseACTION POTENTIAL
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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Characteristics of Action Potentials:a. Minimum stimulus necessary to elicit“threshold” current raises membrane to threshold potentialb. Once stimulated, all-or-none eventc. Propagated over long distances without decrement
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4. Voltage changes during action potentials
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4. Voltage changes during action potentials
EM
Time (msecs)
mVolts
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4. Voltage changes during action potentials
0-20-40-60-80
EM
Time (msecs)
mVolts
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
0-20-40-60-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
1. Resting membrane before arrival
1
0-20-40-60-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
2. Depolarization to 0 mV
1
20
-20-40-60-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
2. Depolarization to 0 mV hyperpolarizing overshoot
1
20
-20-40-60-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
3. Repolarization back to -80 mV
1
2 30
-20-40-60-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
4. Hyperpolarizing afterpotential
1
2 3
4
0-20-40-60-80
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4. Voltage changes during action potentials
EM
Time (msecs)0 1 2 3 4
mVolts
5. Return to resting
1
2 3
4 5
0-20-40-60-80