Host: The Japanese Pharmacological Society
Name : The 96th Annual Meeting of the Japanese Pharmacological Society
Number : 96
Location : [in Japanese]
Date : November 30, 2022 - December 03, 2022
In vascular smooth muscles, the activity of Ca2+-activated Cl- (ClCa) channels regulates the membrane excitability and myogenic tone. TMEM16A channels are predominantly form ClCa currents in vascular smooth muscles including portal vein smooth muscles (PVSMs). Caveola is a cholesterol-rich membrane invaginations and structurally contributes to effective and efficient signal transduction. Caveolin 1 (Cav1) is accumulated in the caveolin and plays a key role in forming the functional complex among enzymes, receptors, and ion channels. In this study, the functional roles of Cav1 on the expression and activity of TMEM16A ClCa channels were examined in portal vein smooth muscle cells (PVSMCs) from wild-type (WT) and Cav1-knockout (KO) mice. Spontaneous contractions of PVSMs were recorded using an isotonic transducer. TMEM16A-mediated ClCa currents were recorded by whole-cell patch-clamp configurations. The expression of TMEM16A channels was quantitatively analyzed by real-time PCR. The amplitude of spontaneous contractions of PVSMs was larger in Cav1-KO mice than WT mice. Whole-cell ClCa currents were also larger in Cav1-KO PVSMCs than WT PVSMCs. Importantly, Ani9 (a specific blocker for TMEM16A channels)-sensitive currents were increased in Cav1-KO PVSMCs compared to WT PVSMCs. The expression of TMEM16A channels was higher in Cav1-KO PVSMs than WT PVSMs. The present data strongly suggest that the caveola structure formed by Cav1 negatively regulates the expression and activity of TMEM16A-mediated ClCa channels in vascular smooth muscle cells.