Smooth muscle cell TMEM16A channels contribute to myogenic constriction in cerebral arteries

Abstract

Transmembrane 16A (TMEM16A) channels are Ca2+‐activated Cl− (ClCa) channels that are expressed in smooth muscle cells of several vascular beds. Physiological functions of vascular TMEM16A channels are unclear. Here, we demonstrate that cell swelling (hypoosmolar bath solution) activates Cl− currents in cerebral artery myocytes. Swelling activated Cl− currents were inhibited by a pore‐targeting TMEM16A antibody, TMEM16A knockdown using siRNA, extracellular Ca2+ removal, and substitution of EGTA for BAPTA in the pipette solution. In contrast, swelling‐activated Cl− currents were not altered by SR Ca2+ load depletion (thapsigargin). TMEM16A knockdown attenuated pressure‐induced vasoconstriction in cerebral arteries when compared to arteries treated with control siRNA. In contrast, TMEM16A knockdown did not alter depolarization (60 mM K+)‐ induced vasoconstriction. These data indicate that membrane stretch activates a local sub‐plasma membrane Ca2+ signal in myocytes that stimulates TMEM16A channels. Such TMEM16A channel activation contributes to the myogenic response in cerebral arteries.