2,3-Butanedione monoxime modifies the glycine-gated chloride current of acutely isolated murine hypothalamic neurons.

In this study, we explored the effect of the chemical phosphatase 2,3-butanedione monoxime (BDM) on glycine current (IGly) of murine ventromedial hypothalamic neurons. Co-application of 0.01 to 67 mM BDM increased IGly decay rate with little change of the peak amplitude. This effect was both rapid in onset and offset and required the presence of the agonist. Pretreatment with BDM alone did not alter-IGly decay. In addition, dialysis of neurons with 500 microM ATP-gamma-S did not alter the acute effect of BDM. Thus, this effect may result from open channel block rather than BDM-induced dephosphorylation of the receptor/channel protein. In contrast to the acute effect described above, relatively prolonged (i.e., greater than 80 s) pretreatment with BDM reduced peak IGly. The phorbol ester (PDBu), a protein kinase C (PKC) activator, mimicked this effect of BDM. Furthermore, chelerythrine, a specific PKC inhibitor, prevented this effect of BDM on peak IGly. Thus, activation of PKC may mediate this attenuating effect of BDM on IGly. For a sub-population of these pretreated neurons, there was a subsequent potentiation of IGly which followed the initial suppressant effect. This potentiation may be due to a phosphatase effect of BDM, since it was observed more frequently when neurons were also pretreated with the protein kinase inhibitors H7 or chelerythrine. These findings suggest that BDM alters protein kinase activity and acts as a phosphatase to regulate the activity of the glycine receptor/channel complex.