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<strong>The TMEM16A channel as a regulator of capillary and arterial function: pharmacology and implications for therapy </strong>

Calcium-activated chloride-channels (CaCCs) are highly expressed in the smooth muscle cells of a range of vital organs and tissues where they provide a depolarising force evoked by a rise in intracellular calcium. In the GI or urogenital tract the channel is primarily active in pacemaking cells that indirectly control the activity of the surrounding smooth muscle. In pericytes, cell that surround capillaries, CaCCs either promote pericyte contraction or lead to spontaneous transient depolarisations that are transmitted to the neighbouring smooth muscle cells. CaCCs are suggested therapeutic targets for a range of disorders, including hypertension, vascular dementia, lower urinary tract symptoms and functional GI disorders. Here, we will present recent advances in the identification of selective small molecule modulators of CaCCs that open up new avenues for the elucidation of coupling between the sarcoplasmic/endoplamic reticulum (SR/ER) and CaCCs in smooth muscles. We will highlight anatomical aspect of SR/ER-CaCC coupling, including the dynamic control of physical interactions between the SR/ER and the plasmalemmal formations in physiology and disease. Current knowledge of the conversion of SR/ER calcium release into smooth muscle excitation will also be covered, focusing on CaCCs to develop a future research as well as therapeutic strategy.

Conversion of SR/ER Ca2+ release into smooth muscle excitation by Ca2+-activated Cl- channels

APPW2025

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[[OD]2S08a-3]The TMEM16A channel as a regulator of capillary and arterial function: pharmacology and implications for therapy

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