Fig. 8.

Fundamental roles of the membrane potential in maintaining the synchrony of spontaneous Ca²⁺ transients.

A: K_v7 voltage-dependent K⁺ (K_v7) channels and inward rectifier K⁺ (K_ir) channels are open under resting condition to hyperpolarise the mural cells. This hyperpolarisation inhibits voltage-dependent IP₃ production and subsequent IP₃ receptor (IP₃R)-mediated Ca²⁺ release and also decreases voltage-dependent Ca²⁺ channel (VDCC)-mediated Ca²⁺ influx and subsequent Ca²⁺-induced Ca²⁺ release via ryanodine receptors (RyR) and/or IP₃R. A resultant decrease in the frequency of spontaneous Ca²⁺ release from the sarcoendoplasmic reticulum (SR/ER) ensures the enough Ca²⁺ refilling in the SR/ER; thus, each spontaneous Ca²⁺ release from SR/ER is large enough to induce Ca²⁺-activated Cl^- channel (CaCC)-mediated depolarisation that leads to recruitment/activation of more store Ca²⁺ release events and their synchronisation within the network of mural cells. B: When the resting membrane potential of mural cells are within the ‘synchronous range’, cyclical spontaneous Ca²⁺ release from SR/ER (blue line) opens CaCCs to induce cyclical spontaneous depolarisation (black line). The depolarisation causes L-type voltage-dependent Ca²⁺ channel (LVDCC)-mediated Ca²⁺ influx (red line). These spontaneous activities spread to neighbouring mural cells via gap junctions. When the resting membrane potential of mural cells are within the ‘quiescent range’, voltage-dependent IP₃ production is suppressed. Thus, cyclical spontaneous Ca²⁺ release from SR/ER is now not generated (blue flat line), and membrane potential change is not detected (black flat line). When the resting membrane potential is higher than the threshold of LVDCC, i.e., within the ‘asynchronous range’, both cyclical spontaneous Ca²⁺ release from SR/ER (blue line) and LVDCC-mediated Ca²⁺ influx (red line) cause high frequency spontaneous Ca²⁺ transients that are generated independently among mural cells.