VYTAUTAS VERSELIS

..The ability of Cx46, and perhaps other connexins, to form functional unapposed hemichannels that are opened by moderate depolarization may represent an unexplored role of connexins as mediators of transport across the plasma membrane...

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..Thus, we demonstrate that both forms of voltage dependence are intrinsic gating mechanisms in Cx46 hemichannels and that the action of external divalent cations is to selectively modulate loop gating...

..These results indicate that metal ions access the cysteine side chains through the open pore and that closure of the loop gate involves movement of the TM1/E1 region that results in local narrowing of the large aqueous connexin pore...

..A number of mutations have been recently reported that map to areas important in gating and permeability and we will undertake functional analyses to examine possible mechanisms of disease associated with Cx46 dysfunction. ..

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..We will characterize the functional properties of humCx46, which have not been reported, and examine the basis of altered or loss of function of Cx46 caused by the N63 substitution. ..

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..A number of mutations have been recently reported that map to areas important in gating and permeability and we will undertake functional analyses to examine possible mechanisms of disease associated with Cx46 dysfunction. ..