Chemical gating of gap junction channels

摘要

Both Ca~(2+) and H~+ play a role in chemical gating of gap junction channels, but, with the possible exception of Cx46 hemichannels, neither of them is likely to induce gating by a direct interaction with connexins. Some evidence suggests that low pHi affects gating via an increase in [Ca~(2+)]_i; in turn, Ca~(2+) is likely to induce gating by activation of CaM, which may act directly as a gating particle. The effective concentrations of both Ca~(2+) and H~+ vary depending on cell type, type of connexin expressed and procedure employed to increase their cytosolic concentrations; however, pHi as high as 7.2 and [Ca~(2+)]_i as low as 150 nM or lower have been reported to be effective in some cells. Some data suggest that Ca~(2+) and H~+ affect gating by acting synergistically, but other data do not support synergism. Chemical gating follows the activation of a slow gate distinct from the fast V_j-sensitive gate, and there is evidence that the chemical/slow gate is V_j-sensitive. At the single channel level, the chemical/slow gate closes the channels slowly and completely, whereas the fast V_j gate closes the channels rapidly and incompletely. At least three molecular models of channel gating have been proposed, but all of them are mostly based on circumstantial evidence.