Title

Mechanosensitivity of gap junction hemichannels

Date of Award

2005

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Physiology and Biophysics

First Committee Member

Gerhard Dahl, Committee Chair

Abstract

Most gap junction hemichannels stay in the closed state before they dock to each other and form complete functional channels. Some exceptions, Connexin 46 (Cx46), Cx50 and pannexin 1, can form functional hemichannels in nonjunctional membranes. These hemichannels are a nonselective conduit to the extracellular medium and may jeopardize cell survival. The physiological function of hemichannels has remained elusive, but it has been postulated that hemichannels are involved in ATP-release caused by mechanical stimulation. In this study, connexin46, carboxyl terminal truncated Cx46 and pannexin are expressed in Xenopus oocytes. With single channel and whole cell electrophysiological studies, we show that these hemichannels are mechanosensitive.The Cx46 hemichannel response to mechanical stress is bipolar. At negative potential stress opens the channel, and at positive potentials stress close it. For two carboxy-terminal truncated mutants, Cx46del249 and Cx46del260, stress can open the hemichannels at any membrane potential. Physiologically, Cx46 and carboxy terminal truncated Cx46 may assist accommodation of the ocular lens by providing a transient path for volume flow as the lens changes shape.The pannexin hemichannel is a large conductance channel and it is permeant for ATP. Membrane stress can open the pannexin 1 hemichannel at both negative and positive potentials. Hence, pannexins are candidates for the release of ATP to the extracellular space upon mechanical stress.

Keywords

Biology, Cell; Biology, Animal Physiology; Biophysics, Medical

Link to Full Text

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