Molecular basis of voltage dependence of connexin channels: an integrative appraisal.

作者: D GONZALEZ , J GOMEZHERNANDEZ , L BARRIO

DOI: 10.1016/J.PBIOMOLBIO.2007.03.007

关键词:

摘要: The importance of electrical and molecular signaling through connexin (Cx) channels is now widely recognized. transfer ions other small molecules between adjacent cells regulated by multiple stimuli, including voltage. Indeed, Cx typically exhibit complex voltage sensitivity. Most are sensitive to the difference cell interiors (or transjunctional voltage, V(j)), while also absolute inside-outside (i.e., membrane potential, V(m)). first part this review focused on description distinct forms sensitivity gating mechanisms that regulate hemichannel activity, both individually as components homotypic heterotypic gap junctions. We then provide an up date precise picture structural aspects how V(j) V(m) sensed, they, therefore, control channel opening closing. Mutagenic strategies coupled with structural, biochemical electrophysical studies providing significant insights into dependence brought about. emerging indicates can undergo transitions conductance states driven voltage-gating mechanisms. Each may contain a set two gates, one fast slow, which mediate main open state residual fully closed state, respectively. Eventually, gate regulates states. Clusters charged residues within separate domains molecule have been identified integral parts sensors. charges at positions amino terminal cytoplasmic domain determine magnitude polarity V(j)-gating, well contributing V(j)-rectifying properties ion permeation. Additionally, important advances made in identifying conformational rearrangements responsible for V(j)-gating Cx43 channel. These changes involve intramolecular particle-receptor interaction carboxy loop.

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