Pacemaker role of pericytes in generating synchronized spontaneous Ca2+ transients in the myenteric microvasculature of the guinea-pig gastric antrum

Abstract

Properties of spontaneous Ca2+ transients in the myenteric microvasculature of the guinea-pig stomach were investigated. Specifically, we explored the spatio-temporal origin of Ca2+ transients and the role of voltage-dependent Ca2+ channels (VDCCs) in their intercellular synchrony using fluorescence Ca2+ imaging and immunohistochemistry.The microvasculature generated spontaneous Ca2+ transients that were independent of both Ca2+ transients in interstitial cells of Cajal (ICC) and neural activity. Spontaneous Ca2+ transients were highly synchronous along the length of microvasculature, and appeared to be initiated in pericytes and spread to arteriolar smooth muscle cells (SMCs). In most cases, the generation or synchrony of Ca2+ transients was not affected by blockers of L-type VDCCs. In nifedipine-treated preparations, synchronous spontaneous Ca2+ transients were readily blocked by Ni2+, mibefradil or ML216, blockers for T-type VDCCs. These blockers also suppressed the known T-type VDCC dependent component of ICC Ca2+ transients or slow waves. Spontaneous Ca2+ transients were also suppressed by caffeine, tetracaine or cyclopiazonic acid (CPA). After the blockade of both L- and T-type VDCCs, asynchronous Ca2+ transients were generated in pericytes on precapillary arterioles and/or capillaries but not in arteriolar SMCs, and were abolished by CPA or nominally Ca2+ free solution.Together these data indicate that pericytes in the myenteric microvasculature may act as the origin of synchronous spontaneous Ca2+ transients. Pericyte Ca2+ transients arise from Ca2+ release from the sarco-endoplasmic reticulum and the opening of T-type Ca2+ VDCCs is required for their synchrony and propagation to arteriolar SMCs.