University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

433

Pages:

3
Author:

Mariam A. A.

Contraction and relaxation of the heart Pacemaker and conduction systems → coordinated excitation → cellular contraction → cardiac contraction Calcium induced calcium release 1. Depolarisation 2. Opening of L-type Ca channels releases Ca from external stores through the T-tubule membrane (20% of Ca supply) 3. Opening of Ryanodine receptor releases Ca from internal stores in the SR (80% of Ca supply) 4. Increased Ca (0.1 → 100μM) 5. Cross-bridge cycling (contractile threshold >0.1 μM) Relaxation 1. Repolarisation 2. Closure of L-type Ca channels (voltage-gated ion channel) 3. Ca is sequestered a. Taken back into the SR via Ca/H ATPase (SERCA2 channel) → 80% b. Extrusion into ECF → 20% i. Sarcolemmal Na/Ca exchanger ii. Sarcolemmal Ca2+ pump 4. Decreasded calcium 5. Calcium dissociates from TnC 6. TnC blocks actin-myosin interactions 7. Relaxation → 2H+ and 2Ca2+/ATP hydrolysed Myocyte APs • Different membrane ion channels exist in different regions of the heart → AP configuration varies • 2 main types of cardiac APs: o Ventricular non-pacemaker ▪ Myocytes (atrium, ventricles) except for pacemaker cells ▪ Fast entry of sodium current → rapid depolarisation o Pacemaker ▪ Slower rate of depolarisation • Resting potential of nodal fibres is less negative (-55mV) than the ventricular muscle fibers (-90 mV) due to leaky Na and Ca channels that allow positive ion inflow • This inactivates voltage-gated Na channels (close when too positive) → delays Na influx → slower depolarisation ▪ SA and atrioventricular nodes of heart ▪ Generated spontaneously Ventricular • Fast upstroke due to Na entry → plateau due to Ca entry → repolarisation due to K exit • • Phase 0: upstroke o Na influx (rapid) o Ca influx (slow) Phase 1: rapid repolarisation o Inactivation of Na current (influx) ▪ Time and voltage related ▪ Activation = open due to depolarisation by AP (0.1-0.2ms) ▪ Inactivation = closed due to hyperpolarisation (~1ms) o Inactivation of transient Ca o Transient K outward current Pacemaker • • • • • • • Phase 2: plateau phase o Continued entry of Ca → L-type (not dominant contribution) o Residual Na influx o Minor Na-Ca exchanger Phase 3: repolarisation component of the action o K efflux Phase 4: electrical diastolic phase • Refractory period (relaxation) • • Phase 0: upstroke o Calcium influx is slow (cf ventricular) o Absence of classical fast sodium cannel Phase 1: rapid repolarisation o Inactivation of calcium o Transient potassium efflux Phase 2: plateau phase is poorly sustained Phase 3: repolarisation due to K+ efflux Phase 4: diastolic potential o Unstable → pacemaker potential o Slow decay of potassium efflux o Depolarisation activated by Ca influx o Hyperpolarisation activated by funny (If) current (combined Na-K current) If pacemaker activity in SA/AV and Purkinje fibres o Mixed Na and K current o Voltage and ligand modulated ▪ Activated by hyperpolarisation (<70-90mV) ▪ cAMP binds to channels to increase their opening rate and probability o o Absolute: from fast upstroke to end of plateau when Na channels close for 100 milliseconds Relative: from end of plateau to after repolarisation ▪ SNS stimulation increases the number of cAMP molecules