The TMEM16A channel represents a key depolarizing mechanism in arterial smooth muscle and contractile pericytes, where it is activated by several endogenous contractile agonists. In this issue of , Mata-Daboin demonstrate a previously unidentified role for TMEM16A in endothelial cells for acetylcholine-mediated vasorelaxation. Collectively, TMEM16A serves as a transducer of vasoactive stimuli to enable fine modulation of vessel tone.
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TMEM16A, a key calcium-activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism of TMEM16A is poorly understood, limiting the discovery of effective modulators. Here, we unveil an allosteric gating mechanism by presenting a high-resolution cryo-EM structure of TMEM16A in complex with a channel inhibitor that we identified, Tamsulosin, which is resolved at 2.
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University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
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Department of Anesthesiology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518034, Guangdong Province, China.
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J Pharmacol Sci
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