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

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.