Cardiac Muscle Physiology (11/8/12)
Compare and contrast the excitation-contraction coupling in cardiac and skeletal muscle
The organization of the membrane system involved in excitation-contraction coupling is similar to that in skeletal muscle. A few diffferences include sparser sarcoplasmic reticulum, t-tubules positioned near Z lines instead of A-I band junctions, t-tubules are larger in diameter, SR makes junctions with t-tubules, dyads in cardiac muscle vs triads in skeletal muscle.
Sliding filament mechanism
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T-SR junction
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Transverse tubular system
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Tropomyosin
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Troponin
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Ventricular muscle action potential
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Acetylcholine
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Actin
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Action potential of pacemaker cells
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Adenosine triphosphate
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Atrial muscle action potential
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Ca2+ ATPase pump
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Ca2+ induced Ca2+ release
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Ca2+ release channels
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Cardiomyopathy
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Contractility
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Desmosomes
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Dihydropyridine (DHP) receptors
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Excitation contraction (EC) coupling
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Frank Starling's Law of the heart
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Gap junctions
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Inotropic state
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Length-tension relationship
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Na+/Ca2+ exchanger
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Pacemaker activity
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Ryanodine receptors (RyR)
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Sarcomeres
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Sarcoplasmic reticulum
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Describe the structural differences between cardiac and skeletal muscle and their importance to the function of these tissues
1. Like skeletal muscle, cardiac muscle is striated, contains the same basic contractile proteins forming thick and thin filaments, organized in sarcomeres, and has the same sliding filament mechanism 2. Cardiac cells contain myofibrils, T-tubules, and SR. Force is controlled by Ca2+ however cardiac muscle is less dependent on the release of Ca2+ from the SR and the mechanism is different (calcium induced calcium release) 3. Cardiac muscle cells depend primarily on oxidative phosphorylation to generate ATP. They are resistant to fatigue and depend on a continuous supply of oxygen 4. Cardiac muscle cells are much shorter than skeletal muscle fibers and are branched. 5. Cardiac muscle cells are joined together by intercalated discs (desmosomes and gap junctions)
Explain the mechanisms of Ca2+ entry and extrusion from cardiac muscle cells
Action potential initiated by pacemaker cells propagates to the sarcolemma and spreads into the T-tubular membrane. Voltage-dependent L-type Ca2+ channels open. This causes Ca2+ induced Ca2+ release from the SR through the ryanodine receptors. This release of Ca2+ from the SR causes cytoplasmic Ca2+ levels to rise. After contraction, Ca2+ is pumped back into the SR via Ca2+ pumps. Ca2+ is pumped back into the extracellular space by the Na+/Ca2+ exchanger
Explain why cardiac muscle cannot be tetanized
Cardiac muscle cannot produce a second action potential until its contraction is almost complete. Because of the slow rise in tension of cardiac muscle, increasing the frequency stimulation (increasing heart rate does not result in temporal summation of tension and cannot produce tetanic contractions in cardiac muscle
Ca2+ channel blockers
Decrease contractility.
Define the mechanical and functional role of the intercalated disc
Desmosomes mechanically adhere cells together Gap junctions electrically connect cells and allow action potentials of one cell to spread to another. This allows the heart to contract as a unit.
Cardiac glycosides
E.g. digitalis. A group of drugs used to treat heart failure. Inhibits Na/K ATPase resulting in accumulation of intracellular Na+. The increased intracellular Na+ is eschanged for extracellular Ca2+ via the Na/Ca exchanger. Increased intracellular Ca2+ leads to increased contractility. More Ca2+ is stored in the SR and more Ca2+ is released from the SR during an action potential.
Describe the effects of the autonomic nervous system on the heart
Increased sympathetic activity (via B2 receptor activation): 1. Increased heart rate, produced by facilitation (phosphorylation) of L-type Ca2+ and pacemaker channels 2. Increased conduction velocity at the AV node, probably due to facilitation of Ca2+ channels 3. Increased force of contraction in atria and ventricles. Results from facilitation of Ca2+ channels 4. Facilitation of delayed rectifier K+ channels and opening of cAMP dependent Cl- channels causes the duration of the cardiac action potential to decrease Parasympathetic activity (M2 muscarinic receptors): 1. Decreased heart rate due to facilitation of ACh activated K+ channels in SA node and inhibition of Ca2+ channels and pacemaker channels 2. Decreased action potential conduction velocity at the AV node (probably due to inhibition of Ca2+ channels and facilitation of K+ channels) 3. Decreased contractility or inotropic state of the atria
Catecholamines
Norepinephrine and epinephrine increase contractility. The primary effect is facilitating Ca2+ channels leading to increased Ca2+ influence. Heart rate is also increased.
Explain the length-tension relationship in cardiac muscle
Same as for skeletal muscle. The major difference is the normal operating range of the two types of muscle. Skeletal muscle normally operates near the peak of its length-tension curve. Cardiac muscle normally works on the ascending portion of the curve at lengths that are shorter than the length at which maximum tension can be developed. This is important because if the heart fills with more blood than usual (which stretches the muscle fibers more than usual), the force generated by the next heartbeat will automatically be increased, resulting in increased ejection of blood. When cardiac muscle is stretched, the passive tension increases substantially, preventing overstretching of the heart.
