Role of capillary pericytes in the integration of spontaneous Ca2+ transients in the suburothelial microvasculature in situ of the mouse bladder
Authors: Hashitani Hikaru , Mitsui Retsu , Miwa‐Nishimura Kyoko , Lam Michelle 
Published: June 2018

Key points

In the bladder suburothelial microvasculature, pericytes in different microvascular segments develop spontaneous Ca2+ transients with or without associated constrictions.

Spontaneous Ca2+ transients in pericytes of all microvascular segments primarily rely on the cycles of Ca2+ uptake and release by the sarco‐ and endoplasmic reticulum.

The synchrony of spontaneous Ca2+ transients in capillary pericytes exclusively relies on the spread of depolarizations resulting from the opening of Ca2+‐activated chloride channels (CaCCs) via gap junctions.

CaCC‐dependent depolarizations further activate L‐type voltage‐dependent Ca2+ channels as required for the synchrony of Ca2+ transients in pericytes of pre‐capillary arterioles, post‐capillary venules and venules.

Capillary pericytes may drive spontaneous Ca2+ transients in pericytes within the suburothelial microvascular network by sending CaCC‐dependent depolarizations via gap junctions.

Mural cells in the microvasculature of visceral organs develop spontaneous Ca2+ transients. However, the mechanisms underlying the integration of these Ca2+ transients within a microvascular unit remain to be clarified. In the present study, the origin of spontaneous Ca2+ transients and their propagation in the bladder suburothelial microvasculature were explored. Cal‐520 fluorescence Ca2+ imaging and immunohistochemistry were carried out on mural cells using mice expressing red fluorescent protein (DsRed) under control of the NG2 promotor. NG2(+) pericytes in both pre‐capillary arterioles (PCAs) and capillaries developed synchronous spontaneous Ca2+ transients. By contrast, although NG2‐DsRed also labelled arteriolar smooth muscle cells, these cells remained quiescent. Both NG2(+) pericytes in post‐capillary venules (PCVs) and NG2(–) venular pericytes exhibited propagated Ca2+ transients. L‐type voltage‐dependent Ca2+ channel (LVDCC) blockade with nifedipine prevented Ca2+ transients or disrupted their synchrony in PCA, PCV and venular pericytes without dis‐synchronizing Ca2+ transients in capillary pericytes. Blockade of gap junctions with carbenoxolone or Ca2+‐activated chloride channels (CaCCs) with 4,4′‐diisothiocyanato‐2,2′‐stilbenedisulphonic acid disodium salt prevented Ca2+ transients in PCA and venular pericytes and disrupted the synchrony of Ca2+ transients in capillary and PCV pericytes. Spontaneous Ca2+ transients in pericytes of all microvascular segments were abolished or suppressed by cyclopiazonic acid, caffeine or tetracaine. The synchrony of Ca2+ transients in capillary pericytes arising from spontaneous Ca2+ release from the sarco‐ and endoplasmic reticulum appears to rely exclusively on CaCC activation, whereas subsequent LVDCC activation is required for the synchrony of Ca2+ transients in pericytes of other microvascular segments. Capillary pericytes may drive spontaneous activity in the suburothelial microvascular unit to facilitate capillary perfusion.