Role of gamma carboxylated Glu47 in connexin 26 hemichannel regulation by extracellular Ca²⁺: insight from a local quantum chemistry study.

ABSTRACT: Connexin hemichannels are regulated by several gating mechanisms, some of which depend critically on the extracellular Ca(2+) concentration ([Ca(2+)]e). It is well established that hemichannel activity is inhibited at normal (∼1 mM) [Ca(2+)]e, whereas lowering [Ca(2+)]e to micromolar levels fosters hemichannel opening. Atomic force microscopy imaging shows significant and reversible changes of pore diameter at the extracellular mouth of Cx26 hemichannels exposed to different [Ca(2+)]e, however, the underlying molecular mechanisms are not fully elucidated. Analysis of the crystal structure of connexin 26 (Cx26) gap junction channels, corroborated by molecular dynamics (MD) simulations, suggests that several negatively charged amino acids create a favorable environment for low-affinity Ca(2+

SUBMITTER: Zonta F 

PROVIDER: S-EPMC3969289 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature