Calcium-activated chloride channels in pericytes and their role in regulating organ blood flow

Pericytes are mural cells of the microvasculature, characterised by a distinctive 'bump-on-a-log' morphology and elongated processes extending along the abluminal surface of capillary and pre- and post-capillary segments. They are widely distributed across organs and exhibit functional heterogeneity. Contractile pericytes directly regulate local blood flow, whereas non-contractile pericytes contribute to electrical signalling by generating depolarising or hyperpolarising events that propagate to upstream vessels and coordinate tissue perfusion. These functions are closely linked to intracellular ion homeostasis. Recent evidence highlights a role for Ca²⁺-activated Cl^- channels (CaCCs), particularly TMEM16A (ANO1), in coupling intracellular Ca^{2 +} signals to membrane depolarisation and pericyte activity. In contractile pericytes, TMEM16A-mediated currents promote depolarisation to activate L-type voltage-gated Ca^{2 +} channels, facilitating Ca²⁺ entry to support contraction. In non-contractile capillary pericytes, periodically generated TMEM16A-dependent depolarisations contribute to the initiation and propagation of spontaneous electrical activity, supporting intercellular synchrony within microvascular networks. Alternatively, asynchronous TMEM16A-dependent depolarisations could sum with each other to maintain resting membrane potentials and basal vascular tone. In this review, we summarise current understanding of CaCC channel function in pericytes across organs, and discuss emerging directions for future research and therapeutic targeting.