TRPM4‐dependent contraction of retinal pericytes (LB846)

Abstract

Pericytes are an integral part of the neurovascular unit and likely contribute to the neuronal‐dependent regulation of capillary blood flow. Like vascular smooth muscle cells (VSMCs), pericytes are thought to contract through membrane depolarization and activation of voltage‐dependent calcium channels which then causes focal constrictions of capillaries. TRPM4, a melastatin transient receptor potential channel, is essential for VSMC membrane depolarization and contraction. Its role in pericyte contraction is not known. We used immunohistochemistry and confocal microscopy to examine the role of TRPM4 channels in pericyte contraction within the mouse retina. We observed TRPM4‐specific immunolabeling in the smooth muscle cells within precapillary arterioles (<10 µm) and in a sub‐population of pericytes surrounding the capillaries most proximal to the arterioles in the mouse retinal vasculature. In addition, we observed constriction in response to the thromboxane A2 analog, 9,11‐dideoxy‐9α,11α‐methanoepoxy prostaglandin F2α (U46619) in pre‐capillary arterioles and in distal and proximal pericyte‐containing capillaries. This response was blocked by the TRPM4 inhibitor 9‐phenanthrol in pre‐capillary arterioles and proximal pericyte‐containing capillaries, but not in pericyte‐containing capillaries distal to feeding arteriole. These findings suggest that TRPM4 plays a role in pericyte constriction within retinal capillary system.Grant Funding Source: HL044455, R37 DK053832, and 1PO1HL095488