Generation of Muscle Tone in the Murine Internal Anal Sphincter by Anoctamin 1
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Authors
Kirchoff, Ileah
Issue Date
2015
Type
Thesis
Language
en_US
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Abstract
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.
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