Roles of endothelial prostaglandin I2 in maintaining synchronous spontaneous Ca2+ transients in rectal capillary pericytes

In hollow visceral organs, capillary pericytes appear to drive spontaneous Ca2+ transients in the upstream arterioles. Here, mechanisms underlying the intercellular synchrony of pericyte Ca2+ transients were explored. Ca2+ dynamics in NG2 chondroitin sulphate proteoglycan (NG2)‐expressing capillary pericytes were examined using rectal mucosa–submucosa preparations of NG2‐GCaMP6 mice. Spontaneous Ca2+ transients arising from endoplasmic reticulum Ca2+ release were synchronously developed amongst capillary pericytes in a gap junction blocker (3 μM carbenoxolone)‐sensitive manner and could spread into upstream vascular segments. Spontaneous Ca2+ transients were suppressed by the Ca2+‐activated Cl− channel (CaCC) blocker niflumic acid and their synchrony was diminished by a TMEM16A inhibitor (3 μM Ani9) in accordance with TMEM16A immunoreactivity in pericytes. In capillaries where cyclooxygenase (COX)‐2 immunoreactivity was expressed in endothelium but not pericytes, non‐selective COX inhibitors (1 μM indomethacin or 10 μM diclofenac) or COX‐2 inhibitor (10 μM NS 398) disrupted the synchrony of spontaneous Ca2+ transients and raised the basal Ca2+ level. Subsequent prostaglandin I2 (PGI2; 100 nM) or the KATP channel opener levcromakalim restored the synchrony with a reduction in the Ca2+ level. PGI2 receptor antagonist (1 μM RO1138452) also disrupted the synchrony of spontaneous Ca2+ transients and increased the basal Ca2+ level. Subsequent levcromakalim restored the synchrony and reversed the Ca2+ rise. Thus, the synchrony of spontaneous Ca2+ transients in pericytes appears to be developed by the spread of spontaneous transient depolarisations arising from the opening of TMEM16A CaCCs. Endothelial PGI2 may play a role in maintaining the synchrony, presumably by stabilising the resting membrane potential in pericytes. Key points Capillary pericytes in the rectal mucosa generate synchronous spontaneous Ca2+ transients that could spread into the upstream vascular segment. Spontaneous Ca2+ release from the endoplasmic reticulum (ER) triggers the opening of Ca2+‐activated Cl− channel TMEM16A and resultant depolarisations that spread amongst pericytes via gap junctions, establishing the synchrony of spontaneous Ca2+ transients in pericytes. Prostaglandin I2 (PGI2), which is constitutively produced by the endothelium depending on cyclooxygenase‐2, appears to prevent premature ER Ca2+ releases in the pericytes allowing periodic, regenerative Ca2+ releases. Endothelia