Reversible blockade of gap junctional communication by 2,3-butanedione monoxime in rat cardiac myocytes

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Abstract
2,3-Butanedione monoxime (BDM), a nucleophilic agent endowed with a “phosphatase-like” activity, is often used as a tool for investigating the effects of changes in phosphorylation level of protein constituents on membrane channel function. BDM produced a rapid, dosc-dependent, and reversible abolition of the cytosolic continuity existing between cells via gap junctional channels. The persistence of this effect when a nonhydrolyzable analogue of ATP [adenosine 5'-O-(3-thiotriphosphate) (ATP(gamma)S)] was introduced in the cytosol suggests that the acute suppressant effect of BDM was not due to dephosphorylation. However, the higher reversibility after BDM withdrawal in presence of ATP(gamma)S could signify that a protein-dephosphorylating activity gradually occurred during the oxime treatment. Junctional uncoupling took place even when the moderate increase in cytosolic Ca2+ concentration induced by BDM was prevented by ryanodine. These results are consistent with the model of dual mechanism of BDM action proposed for some other membrane channels, consisting of a quick channel block and a parallel slow inhibition, plausibly through dephosphorylation.