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- W2163145087 abstract "Background Transient receptor potential C3 ( TRPC 3) has been demonstrated to be involved in the regulation of vascular tone through endothelial cell ( EC ) hyperpolarization and endothelium‐dependent hyperpolarization–mediated vasodilation. However, the mechanism by which TRPC 3 regulates these processes remains unresolved. We tested the hypothesis that endothelial receptor stimulation triggers rapid TRPC 3 trafficking to the plasma membrane, where it provides the source of Ca 2+ influx for small conductance calcium‐activated K + (SK Ca ) channel activation and sustained EC hyperpolarization. Methods and Results Pressurized artery studies were performed with isolated mouse posterior cerebral artery. Treatment with a selective TRPC 3 blocker (Pyr3) produced significant attenuation of endothelium‐dependent hyperpolarization–mediated vasodilation and endothelial Ca 2+ response ( EC ‐specific Ca 2+ biosensor) to intraluminal ATP . Pyr3 treatment also resulted in a reduced ATP ‐stimulated global Ca 2+ and Ca 2+ influx in primary cultures of cerebral endothelial cells. Patch‐clamp studies with freshly isolated cerebral EC s demonstrated 2 components of EC hyperpolarization and K + current activation in response to ATP . The early phase was dependent on intermediate conductance calcium‐activated K + channel activation, whereas the later sustained phase relied on SK C a channel activation. The SK C a channel–dependent phase was completely blocked with TRPC 3 channel inhibition or in ECs of TRPC 3 knockout mice and correlated with increased trafficking of TRPC 3 (but not SK C a channel) to the plasma membrane. Conclusions We propose that TRPC 3 dynamically regulates SK C a channel activation through receptor‐dependent trafficking to the plasma membrane, where it provides the source of Ca 2+ influx for sustained SK C a channel activation, EC hyperpolarization, and endothelium‐dependent hyperpolarization–mediated vasodilation." @default.
- W2163145087 created "2016-06-24" @default.
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- W2163145087 date "2014-08-15" @default.
- W2163145087 modified "2023-09-27" @default.
- W2163145087 title "Activation of Endothelial Transient Receptor Potential C3 Channel Is Required for Small Conductance Calcium‐Activated Potassium Channel Activation and Sustained Endothelial Hyperpolarization and Vasodilation of Cerebral Artery" @default.
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- W2163145087 doi "https://doi.org/10.1161/jaha.114.000913" @default.
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