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

摘要

Mural cells in precapillary arterioles (PCAs) generate spontaneous Ca2+ transients primarily arising from the periodic release of Ca2+ from sarcoendoplasmic reticulum (SR/ER). The Ca2+ release induces Ca2+-activated chloride channel (CaCC)-dependent depolarisations that spread to neighbouring mural cells to develop the synchrony of their Ca2+ transients. Here, we explored the roles of K+ channels in maintaining the synchrony of spontaneous Ca2+ transients. Intracellular Ca2+ dynamics in mural cells were visualised by Cal-520 fluorescence Ca2+ imaging in the submucosal PCAs of rat rectum. Increasing extracellular K+ concentration ([K+](o)) from 5.9 to 29.7mM converted synchronous spontaneous Ca2+ transients into asynchronous, high-frequency Ca2+ transients. Similarly, the blockade of inward rectifier K+ (K-ir) channels with Ba2+ (50M) or K(v)7 voltage-dependent K+ (K(v)7) channels with XE 991 (10M) disrupted the synchrony of spontaneous Ca2+ transients, while the blockers for large-, intermediate- or small-conductance Ca2+-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 Ba2+, nifedipine (1M) attenuated the asynchronous Ca2+ transients but failed to restore their synchrony. In contrast, levcromakalim, an ATP-sensitive K+ channel opener, restored the synchronous Ca2+ 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' Ca2+ transients to ensure sufficient SR/ER Ca2+ refilling that is required for regenerative Ca2+ release resulting in synchronous Ca2+ transients amongst the mural cells.