Cardiac Muscle

1. Electrical synapse: Direct Transmission

a. b. Gap Junctions Nexus Connexon channels: multilayer ion channels

2. Excitation contraction coupling is the same as in skeletal muscle except there are a few differences a. Review of skeletal muscle contraction
i. AP propagation into T-Tubules (Excitation) ii. An action potential in the sarcolemma (skeletal muscle cell membrane) travels down the transverse tubules (T-tubules) deep into the interior of the muscle cell. (Excitation) iii. DHP receptor tugs on Ryanodine Receptor and Ca2+ is released through RyR iv. Ca2+ activates the thin filament by binding to troponin C and making conformational change on tropomysosin v. Cross-Bridge Cycling (Contraction) vi. Ca2+ ATPase actively transports Ca2+ back into SR and the removal of Ca2+ inactivates the thin filament.

b. Activation of AP
i. Automaticity in the heart 1. electrical automaticity= heart spontaneously generates the membrane AP for each heart

2.

Pacemaker cells a. Slow-response (nodal) AP i. sinoatrial (SA) node and atrioventricular (AV) node 1. have no true resting membrane potential ii. Phases: 1. Phase 0: (slow depolarization) a. opening of voltage-dependent slow L-type Ca2+ channels i. Ca2+ Influx 2. Phase 3 (repolarization) a. closure of L-type Ca2+ channels and opening of K+ channels i. K+ Efflux 3. Phase 4 (pacemaker potential)- slow depolarization a. Closure of K+ channels and the opening of funny (If) channels i. Na+ influx b. T-type Ca2+ channels and L-type Ca2+ channels i. Ca2+ influx

b.

Fast- response (ventricular/atrial myocyte) AP i. Phases: 1. Phase 0 (depolarization) a. opening of fast voltage-dependent Na+ channels i. Na+ influx 2. Phase 1 (early repolarization) a. Closure of fast voltage-dependent Na+ channels and the opening of voltagedependent K+ channels i. efflux K+ 3. Phase 2 (plateau) a. Opening of voltage dependant slow L-type Ca2+ channels balance with slow delayed rectifier K+ channels i. Influx Ca2+, Efflux K+ 4. Phase 3 (rapid repolarization) a. Closure of L-type Ca2+ channels and the opening of several K+ channels i. efflux K+ 5. Phase 4 (resting membrane potential) a. both delayed K+ rectifier channels close, but the inward K+ rectifier channels (efflux of K+) remain open and maintain the resting membrane potential

c. Ca2+ Release
i. Calcium-induced-calcium-release: extracellular Ca2+ needed for contraction because it opens RyR-2 receptors Ca2+ released into sarcoplasm from SR

d. Cytoplasmic [Ca2+] is lowered in 3 ways:

i. 1. As in skeletal muscle, Ca2+ is returned to the SR via the SR Ca2+-ATPase (SERCA) pump (primary active transport) located in the SR membrane. Calsequestrin binds Ca2+ inside SR. ii. 2. Ca2+ is pumped out of the cell by a PM Ca2+-ATPase (PMCA) pump (primary active transport) iii. 3. Ca2+ is moved out of cell via a Na+o-Ca2+i (3 Na in, 1 Ca out) exchanger (secondary + active transport; antiporter) located in the cell membrane. Na/K ATPase keeps the Na concentration favorable for this ion exchange.

iv.

3. Uses and Sources of ATP a. Uses:

i. ATP powers the crossbridge cycle, needed for every contraction ii. ATP used in relaxation (SERCA, PMCA, and Na+/Ca2+ exchanger with Na+/K+ ATPase) iii. Sometimes it is used in the production of cyclic AMP

b. Sources:
i. aerobic metabolism (oxidative phosphorylation) and requires a constant supply of blood ii. The primary metabolic substrates utilized by the heart are fatty acids and lactate

4. Cardiac Muscle Mechanics

a. Duration of the APs and contraction i. Unlike skeletal muscle, cardiac muscle contractions cant summate no tetanic contraction. ii. APs in cardiac muscle are very long in duration 1. cytoplasmic Ca2+ remains longer so contraction lasts longer 2. for every contraction period (systole), there is a resting period (diastole) so the heart can refill with blood

b.

Length-Tension Relationship i. passive tension in cardiac, the rest length is shorter than skeletal 1. *reminder of passive tension* The force generated by stretching the connective
material; it does not require the breakdown of ATP. Remember that cardiac muscle cells are connected by intercalated discs to form a hollow organ that rhythmically fills and empties. During the filling phase of the heart, called diastole, muscle cells are relaxed (cytoplasmic Ca2+ is very low) and the entering blood stretches the cardiac cells, increasing the volume of the chamber. This generates passive tension. Because the ventricle is a hollow structure, muscle length is equivalent to ventricular volume, which is equivalent to diastolic volume (the volume during diastole). The volume in the ventricle at the end of the diastolic phase is called the End Diastolic Volume or the Preload.

ii. Total tension in cardiac versus skeletal iii. Active tension is the additional tension produced by the interaction of actin and myosin. iv. optimal length (max active tension) represents the muscle length at which the myocytes can generate their most forceful contraction 1. the normal working range indicates the stretched length (preload) of a normal ventricle at rest, referred to as the rest length. Notice that resting cardiac muscle is NOT at its optimal length for active force development.

c.

Force-Velocity Relationship i. As stretched length (preload) increases, the force-velocity curves shifts up and to the right. With increased preload, muscle can lift a given afterload (e.g. 0.5) at a faster rate. For the heart this means that if the ventricle fills more (increased preload), it will be able to eject blood faster at a given aortic pressure (i.e. afterload)

5. Adrenergic Receptor Signaling

a. b. a. beta-2 adrenergic receptor (2 adrenoreceptor) leads to heart muscle contraction from adrenaline Digitalis i. improves cardiac contractility ii. binds to Na-K ATPase pump on cardiac cell membrane inhibits pump and intracellular [Na+] iii. Ca2+ is not extruded as effectively from the cell contractility

6. Clinical Correlation

Extra picture for muscle cell contraction