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Generation of Muscle Tone in the Murine Internal Anal Sphincter by Anoctamin 1
AdvisorKeef, Kathleen D.
Biochemistry and Molecular Biology
Biochem and Molecular Biology
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Maintenance of normal muscle tone in the internal anal sphincter is important to prevent medical disorders related to incontinence. Recently, it has been found that a calcium activated chloride channel found in interstitial cells of cajal, anoctamin 1, has a role in the generation of slow waves in smooth muscle cells. In this study, the role of anoctamin 1 in the generation of muscle tone in the internal anal sphincter was further investigated. Electrophysiology measurements confirmed that slow waves were entirely abolished when the murine internal anal sphincter was exposed to T16AinhA01, a known inhibitor of anoctamin 1. According to strain gauge measurements, muscle tone decreased in a dosedependent manner in the presence of T16AinhA01. Furthermore, inhibiting Ltype calcium channels in smooth muscle with nifedipine also resulted in dose dependent smooth muscle relaxation. This data leads to the conclusion that muscle tone in the murine internal anal sphincter results from depolarization of the interstitial cells of cajal by the efflux of chloride through anoctamin 1, and propogation of this signal within the smooth muscle via LType calcium channels.