A Human Disease Mutation (D50N) Reveals Insights on the Mechanisms for Ca2+ Regulation in Human Connexin26 (hCX26) Hemichannels

Abstract

j = 0. The macroscopic G j showed substantial reduction (by 82% at V j = 100mV) when depolarizing Cx50expressing cell, whereas a moderate reduction (by 61% at V j = À100mV) when hyperpolarizing Cx50-expressing cell. This observation is in agreement with previous finding that Cx50 hemichannel gates when the cell is depolarized. Single Cx50/Cx50Cx36N heterotypic channel displayed a main conductance of 120pS at low V j pulses (5 20mV), but the conductance rectified with increasing V j pulses. Cx50/Cx50N9R heterotypic GJ channel also exhibited asymmetrical V jgating properties at macroscopic level, and single channel recordings indicated a main conductance of~150pS at V j = 20mV. These results demonstrate that the V j -gating properties and unitary conductance of Cx50 hemichannels were evidently modified when docking with Cx50-Cx36N or Cx50N9R mutants. These novel properties of heterotypic channels provide insights into the V j -gating mechanisms of Cx50 GJ channels.