Myocardium, heartbeat and cardiac output

Chapter 12

pages 361 - 367, 372 - 375

Myocardium (cardiac muscle)

Heart is myocardium lined with endothelial cells facing blood Myocardium combines properties of skeletal and smooth

muscle Same sarcomere structure as skeletal muscle with light and

dark bands Fibers are shorter and have more branching when compared to

skeletal muscle fibers

Excitation-contraction coupling is regulated by troponin and tropomyosin as in skeletal muscle Smooth muscle myosin needs Ca2+-calmodulin complex to hydrolyze

ATP

Join adjacent cardiac muscle cells

Hold the cells togetherand myofibrils attach to

Figure 9-39

Myocardium (cardiac muscle)

Electrical conduction is similar to smooth muscle No external innervation, neuromuscular junction, or

ligand-gated AChRs required as in skeletal muscle Some myocardial fibers undergo spontaneous

pacemaker activity without external input Many fibers are connected via gap junctions like

smooth muscle to conduct pacemaker potentials

Myocardium (cardiac muscle)

Spontaneous activity and other contractile machinery modulated by hormones and neurotransmitters to alter cardiac output

Epinephrine/norepinephrine – adrenergic receptors (GPCRs)

Acetylcholine – muscarinic AChRs (GPCRs) Nicotinic AChRs are ligand-gated ion channels in

neuromuscular junction

Which of the following are found in both cardiac and skeletal muscle fibers?

1 2 3 4 5

20% 20% 20%20%20%1. Gap junctions

2. Sarcomeres

3. Nicotinic AChRs

4. Muscarinic AChRs

5. -adrenergic receptors

Electrical conduction in heart

Heart contains non-contractile myocardium for heartbeat coordination Approximately 1% of myocardial fibers are non-contractile

Extensively connected by gap junctions Remember that depolarization of one cell can be rapidly

transmitted to a second cell via ion flow through gap junction channels

Spread wave of electrical excitation and coordinate contraction of contractile myocardium

Conducting system ofthe heart

P atria contractQRS ventricles contract

T ventriclesrepolarize

Sequence of cardiac excitation

Pacemaker potentials and myocardial excitability

Spontaneous APs in SA node do not require external depolarization

Peripheral nerves and skeletal muscle require synaptic transmission and EPSPs

SA node will spontaneously depolarize at rest without external excitation

Membrane potential fromcardiac node cell

Membrane potential fromventricular muscle cell

Pacemaker potentials and myocardial excitability

Unlike SA node, APs in contractile myocardium still require external source of depolarization

This external depolarization is provided by gap junctions

APs in contractile myocardium have much longer duration than skeletal muscle and peripheral nerves

Long AP functions to produced sustained contraction instead of a twitch

Excitation-contraction coupling

Some differences between cardiac and skeletal muscle excitation-contraction coupling

External Ca2+ required Larger fraction of cytosolic Ca2+ comes from

VGCCs (voltage gated calcium channels) that remain open during plateau AP

Excitation-contraction coupling

SR does not encircle cardiac A-M filament bundles Not all A-M filaments available for cycling during

cardiac AP Strength of contraction modulated by increasing

Ca2+ not by tetanus or recruiting fibers Longer refractory period of cardiac muscle

Excitation-contractionCoupling in CardiacMuscle

L-type Ca channelsmeans “long lastingcurrent”, so this prolongsthe AP and the twitch ascompared to skeletalmuscle

Timing of AP and twitch tension in Skeletal and Cardiac Muscle

Electrocardiogram (ECG or EKG) records electrical signals produced by myocardial tissue due cardiac cycle

Coordinated contraction of heart muscle produces an large electrical signal due to bulk ion flow

Voltage changes due to bulk ion flow can be recorded with surface electrodes

EKG amplitude is proportional to V(t) and dV/dt Characteristic waveform is observed and can be

used to diagnose problems

Electrocardiogram

Typical EKG

EKG in Healthy Person & 2 Cases of AV Block

Partial block, every other atrial impulse works

Total block, ventricles driven by slow pacemaker cellin bundle of His

Cardiac output

The average flow rate of blood through heart per minute is known as cardiac output (CO)

CO is product of SV (stroke volume) and heart rate (HR) CO = SV x HR Can control heart rate and stroke volume to change

cardiac output during rest or periods of intense activity Heart rate change be modulated by altering

excitability of pacemaker cells

Cardiac output

SV = EDV – ESV, can change SV in two ways Systemic vasculature can control amount of blood

returned to ventricle following diastole (EDV) Ventricular contractility can control amount of blood left in

ventricle following systole (ESV) Control of CO is accomplished via autonomic

nervous system Parasympathetic system decreases CO Sympathetic system increases CO

Control of heart rate

Normal heart will beat around 100 beats/min without any autonomic innervation

Numerous sympathetic and parasympathetic efferents terminate in SA node

At rest, parasympathetic system is more active so resting HR is 70 beats/min, below inherent rate of 100 beats/min

Control of heart rate

Sympathetic system increases HR by increasing inward cation (If) and low-threshold T-type Ca2+ currents in SA node Larger inward current increases rate of spontaneous

depolarization Parasympathetic fibers decrease HR by decreasing

If and T-type Ca2+ currents Parasympathetic fibers also increase K+ channel

activity Smaller inward current reduces rate of spontaneous

depolarization

Effects of sympathetic and parasympathetic nerveson SA nodal cell

Major factors that affect the heart rate

Signal Transduction Review

GPCRs and heart rate

Activation of GPCRs will effect contractility and heart rate via modulation of voltage-gated ion channels

Sympathetic increase of heart rate NE → adrenergic GPCR → activates adenylyl cyclase → increases

cAMP → activates PKA → increased phosphorylation of If and T-type channels → more inward current → increased dVm/dt

Phosphorylated channels are more likely to open at “resting” Vm

Parasympathetic decrease of heart rate ACh → mAChR GPCR → inhibits adenylyl cyclase → decreases

cAMP → deactivates PKA → decreased phosphorylation of If and T-type channels → less inward current → decreased dVm/dt

Dephosphorylated channels are less likely to open at “resting” Vm

Control of stroke volume – ventricular filling

Changes in EDV and ESV affect SV Remember SV = EDV – ESV EDV alters ability of ventricles to eject blood Relationship between SV and EDV is called Frank-

Starling mechanism Consequence of relationship between muscle fiber

length and tension Stretched cardiac muscle generates more tension

Ventricular Function Curve, EDV is major determinant ofventricular stretch which yields more forceful contraction

Control of stroke volume – ventricular filling

Therefore filling ventricles more will increase ability of ventricles to eject blood

Direct relationship venous return → atrial volume → ventricular filling → EDV → SV

Main function is to make sure pulmonary and systemic blood flows are equal

Prevents accumulation of blood in pulmonary or systemic vessels

Control of stroke volume - afterload

Increased arterial pressure increases ESV (end

systolic volume) Increased arterial pressure will shorten ventricular

ejection Valve closes when Parterial > Pventricle

Less time to eject blood from ventricle during single cycle, so stroke volume decreases

Control of stroke volume - afterload

If blood pressure is elevated, heart must work harder to eject same amount of fluid

This requires increased ventricular contractility Arteries can control systemic pressures via

constriction and dilation Preload – venous return that fills ventricle to

increase SV Afterload – arterial pressure that heart must work

against or result is decrease in SV Changes in SV due to preload and afterload are

“passive” effects

Control of stroke volume - contractility

EDV is somewhat affected by atrial contractility ESV is controlled by ventricular contractility Contractility changes are “active”, affected by

sympathetic and parasympathetic innervation Reflects increased myocardial activity independent

of length-tension relation

Sympathetic stimulation causes increased contractility ofventricular muscle

Rate of force development andrelaxation increase as well asthe force developed

Control of stroke volume - contractility

Main target is control of Ca2+ influx through VGCCs (voltage gated calcium channels) and CICR (calcium induced calcium release)

Atrial myocardium has sympathetic and parasympathetic innervation mAChRs and adrenergic GPCRs

Ventricular myocardium only has sympathetic innervation adrenergic GPCRs

Mechanisms of sympathetic effects oncardiac muscle contractility

Major factors determining cardiac output. Reversal of arrowsillustrate how cardiac output is decreased