2016B02 Compare and contrast the actional potentials from the sino-atrial node and a ventricular myocyte.

· Intro

· Graphs and conductances

· Pacemaker action potential

· Ventricular myocyte action potential

· Allows rapid, co-ordinated signalling

· Rapid depolarisation followed by repolarization

· Ion channels cycle through resting -> activated -> inactivated states

Determinants of ion flux

· Channel permeability: voltage dependent

· Electrochemical gradients

o Na⁺ and Ca²⁺ into cell, K⁺ out of cell

o Mainly due to Na⁺K⁺ATPase

Features	· Automaticity o i.e. intrinsic, rhythmic, frequent depolaristion and contraction o HCN channel produces ‘funny current’ – i.e. mixed Na⁺ and K⁺ influx o [cAMP] ∝ I_f ∝ slope of phase 4 ∝ heart rate o Note depth of repolarisation ∝ I_K ∝ 1/(heart rate) · Post-repolarisation refractoriness o RRP extends into phase 4
Refractory periods	· Effective (ERP): insufficient HCN and Ca²⁺ channels resting; action potential (AP) impossible · Relative (RRP): enough HCN and Ca²⁺ channels resting but fewer than normal; AP possible with higher than normal stimulus
Factors increasing rate	· ↑SNS -> ↑I_f = ↑I_Ca > I_K -> ↑steepness all slopes, especially phase 4 · ↑Temp -> ↑cell metabolic rate (enzymes, pumps) · ↓K⁺ -> less hyperpolarisation · Neonate: ↑resting HR (fixed stroke volume)
Factors decreasing rate	· ↑PSNS: -> ↓I_f, ↑I_K -> ↓steepness phase 4, increased hyperpolarisation · ↓Temp -> ↓cell metabolic rate (enzymes, pumps) · Hypoxia -> failure of Na⁺K⁺ATPase, unable to repolarize cell, HCN not reactivated · Elderly: fibrous/fatty change in conduction system, ↓β₁ adrenoceptors

Features	· Plateau -> time for systolic ejection and prevention of tetany · Variable timing -> co-ordinated contraction o e.g. endocardial cells start earlier, finish later
Refractory periods	· Absolute (ARP):no Na⁺ channels resting; AP impossible · Effective (ERP): insufficient Na⁺ channels resting; AP impossible · Relative (RRP): enough Na⁺ channels resting, but fewer than normal; AP possible with higher than normal stimulus · Supranormal period (SNP): AP possible with lower than normal stimulus (? closer to threshold potential ? other mechanism)
Autonomic changes	· SNS: ↓ duration of action potential (phosphorylation of phospholamban -> ↑Ca²⁺ reuptake)
Pathological changes	· Hypoxia: failure of Na⁺K⁺ATPase -> depolarisation to -50mV -> inactivation of fast-Na⁺ channel and activation of L-Ca²⁺ channel -> behaves like pacemaker cell -> arrhythmia