Role of K+ channels in maintaining the synchrony of spontaneous Ca2+ transients in the mural cells of rat rectal submucosal arterioles

Mural cells in precapillary arterioles (PCAs) generate spontaneous Ca 2+ transients primarily arising from the periodic release of Ca 2+ from sarcoendoplasmic reticulum (SR/ER). The Ca 2+ release induces Ca 2+ -activated chloride channel (CaCC)-dependent depolarisations that spread to neighbouring mural cells to develop the synchrony of their Ca 2+ transients. Here, we explored the roles of K + channels in maintaining the synchrony of spontaneous Ca 2+ transients. Intracellular Ca 2+ dynamics in mural cells were visualised by Cal-520 fluorescence Ca 2+ imaging in the submucosal PCAs of rat rectum. Increasing extracellular K + concentration ([K + ] o ) from 5.9 to 29.7 mM converted synchronous spontaneous Ca 2+ transients into asynchronous, high-frequency Ca 2+ transients. Similarly, the blockade of inward rectifier K + (K ir ) channels with Ba 2+ (50 μM) or K v 7 voltage-dependent K + (K v 7) channels with XE 991 (10 μM) disrupted the synchrony of spontaneous Ca 2+ transients, while the blockers for large-, intermediate- or small-conductance Ca 2+ -activated K + channels had no effect. K ir 2.1 immunoreactivity was detected in the arteriolar endothelium but not mural cells. In the PCAs that had been pretreated with XE 991 or Ba 2+ , nifedipine (1 μM) attenuated the asynchronous Ca 2+ transients but failed to restore their synchrony. In contrast, levcromakalim, an ATP-sensitive K + channel opener, restored the synchronous Ca 2+ transients. Thus, constitutively active K v 7 and K ir channels appear to be involved in maintaining the relatively hyperpolarised membrane of mural cells. The hyperpolarised membrane prevents depolarisation-induced ‘premature’ Ca 2+ transients to ensure sufficient SR/ER Ca 2+ refilling that is required for regenerative Ca 2+ release resulting in synchronous Ca 2+ transients amongst the mural cells.