Effects of ATP-sensitive K(+)-channel activators on transmitter release parameters at the frog neuromuscular junction

The frog neuromuscular junction was used to study KATP channel action and its relation to transmitter release. Diazoxide (10 microM) and cromakalim (300 microM) decreased the amplitude of the end-plate potential (EPP) without significantly affecting the miniature end plate potential (MEPP) amplitude. Thus, there was a significant decrease in the quantal content of EPP after administration of the KATP channel activators. These agents did not alter MEPP frequency or resting membrane potential (RMP). The diazoxide-induced decrease in EPP amplitude was antagonized by the KATP blocker glibenclamide (10 microM) suggesting KATP channel involvement. Glibenclamide (10 microM) by itself caused a significant decrease in the RMP without significantly affecting the parameters of transmitter release. The diazoxide-induced decrease in EPP amplitude was not readily reversible with washing, however, when glibenclamide was added after diazoxide, the effect was easier to reverse. The results indicate that the activators exert their effect predominantly at the presynaptic region.