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

Properties of spontaneous Ca(2+) transients in the myenteric microvasculature of the guinea-pig stomach were investigated. Specifically, we explored the spatio-temporal origin of Ca(2+) transients and the role of voltage-dependent Ca(2+) channels (VDCCs) in their intercellular synchrony using fluorescence Ca(2+) imaging and immunohistochemistry. The microvasculature generated spontaneous Ca(2+) transients that were independent of both Ca(2+) transients in interstitial cells of Cajal (ICC) and neural activity. Spontaneous Ca(2+) 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 Ca(2+) transients was not affected by blockers of L-type VDCCs. In nifedipine-treated preparations, synchronous spontaneous Ca(2+) transients were readily blocked by Ni(2+), mibefradil or ML216, blockers for T-type VDCCs. These blockers also suppressed the known T-type VDCC dependent component of ICC Ca(2+) transients or slow waves. Spontaneous Ca(2+) transients were also suppressed by caffeine, tetracaine or cyclopiazonic acid (CPA). After the blockade of both L- and T-type VDCCs, asynchronous Ca(2+) transients were generated in pericytes on precapillary arterioles and/or capillaries but not in arteriolar SMCs, and were abolished by CPA or nominally Ca(2+) free solution. Together these data indicate that pericytes in the myenteric microvasculature may act as the origin of synchronous spontaneous Ca(2+) transients. Pericyte Ca(2+) transients arise from Ca(2+) release from the sarco-endoplasmic reticulum and the opening of T-type Ca(2+) VDCCs is required for their synchrony and propagation to arteriolar SMCs.