Figure 3.

Schematic of sinus node membrane potential and underlying mechanisms. Top: action potential (AP) of a rabbit sinoatrial nodal myocyte (red). Middle: different components of the “membrane clock.” Bottom: different components of the “Ca²⁺ clock.” During phase 4, cytosolic [Ca²⁺] increases due to spontaneous Ca²⁺ releases from the sarcoplasmic reticulum (SR) (dark blue). Activation of L-type Ca²⁺ channels (orange) then causes Ca²⁺-induced Ca²⁺ release from the SR, resulting in the whole cell Ca²⁺ transient. Cytoplasmic Ca²⁺ is removed by the sarco(endo)plasmic reticulum calcium ATPase (SERCA) pump (gray) and by sodium-calcium exchanger (NCX) (blue). DD, diastolic depolarization; I_Ca,T, T-type voltage-dependent Ca²⁺ current; I_Ca2,L, L-type voltage-dependent Ca²⁺ current; I_f, funny current; I_NCX, sodium-calcium exchange current; I_K, delayed rectifier potassium current; LCRs, local Ca²⁺ releases; MDP, maximum diastolic potential. Reproduced from Ref. 79 with permission.