Pre- and postsynaptic ATP-sensitive potassium channels during metabolic inhibition of rat hippocampal CA1 neurons

Presynaptic and postsynaptic membrane activities during experimental metabolic inhibition were analysed in mechanically dissociated rat hippocampaCN, an inhibitor of mitochondrial ATP synthesis, induced an outward current across the postsl neurons using nystatin-perforated and conventional whole-cell patch clamp recordings. Naynaptic soma membrane. This current was blocked by tolbutamide, a sulfonylurea, which blocks ATP-sensitive K+ (K-ATP) channels. The presynaptic effect of metabolic inhibitors such as NaCN, NaN3, or glucose-free solution was to increase the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs). Tolbutamide had no effect on this increase in mIPSC frequency induced by metabolic inhibition. Diazoxide, a K-ATP channel opener, evoked a similar somatic outward current in a dose-dependent manner. In addition, diazoxide decreased the frequency of mIPSCs in a dose-dependent fashion. Both these pre- and postsynaptic effects of diazoxide were reversed by tolbutamide, suggesting the existence of K-ATP channels on both pre- and postsynaptic membranes. These results confirm the presence of K-ATP channels on both the pre- and postsynaptic membranes but indicate that the channels have significantly different sensitivities to metabolic inhibition.