Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Donglin Bai

Abstract

The interface of the first transmembrane domain and the first extracellular loop (TM1/E1 border) in several gap junction (GJ) channels is known to line a portion of the pore and plays an important role in determining GJ channel properties. By introduction of a charged residue into this domain of Cx50, the resultant mutant channels showed drastically altered unitary conductance (γj) and transjunctional voltage-dependent gating (Vj-gating). Specifically G46D and G46E increased the Cx50 γj from 201 to 256 and 293 pS, respectively and G46K channel showed a decreased γj of only 20 pS. Moreover, in single channel recordings of homotypic G46K and heterotypic Cx50/G46K channels, only loop gating transitions were observed, indicating an apparent loss of fast Vj-dependent gating transitions. The homology structural models indicate that the pore surface electrostatic potential at the TM1/E1 border is a dictating factor in determining efficiency of ion permeation and Vj-gating of Cx50 GJ channels.


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