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A new paper, published by the Tammaro lab in the Proceedings of the National Academy of Sciences (PNAS), shines new light on potential sites for pharmacological intervention within TMEM16A channels.

The TMEM16A calcium-activated chloride channels are involved in vital physiological functions, including the control of artery tone and nociception. Dysfunction of these ion channels leads to pathology; thus, they are proposed therapeutic targets. In spite of this, our knowledge of TMEM16A pharmacology lags behind that of other ion channels. Defining the mode of action and binding sites for synthetic test compounds lays the foundation for the development of new TMEM16A-interacting drugs.

The Tammaro Lab and collaborators demonstrate that intracellular calcium triggers a conformational change in the outer mouth of the channel, which enables entry of small molecules into the pore. The explanation of this structural rearrangement demonstrates a crucial site for pharmacological intervention and sheds light on a new aspect of calcium-gating in the TMEM16A channel. The study is published in PNAS (An outer-pore gate modulates the pharmacology of the TMEM16A channel | PNAS)

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