Pre-synaptic effect of the ATP-sensitive potassium channel opener diazoxide on rat substantia nigra pars reticulata neurons

Abstract

Spontaneous synaptic currents were recorded from visually identified substantia nigra pars reticulata (SNR) neurons in the rat brain slice preparation by whole-cell patch clamp technique. GABA neurons were distinguished from dopamine neurons by their electrophysiological characteristics. In the presence of 20 μM AP5 and CNQX, the spontaneous synaptic currents recorded from GABA neurons were sensitive to bicuculline and reversed polarity at a potential close to the equilibrium potential of Cl , indicating that they were mediated by GABA(A) receptors. TTX at 1 μM eliminated action potential-dependent release of GABA from nerve terminals, revealing the miniature inhibitory post-synaptic currents (mIPSCs). The ATP-sensitive potassium channel (K(ATP) channel) opener diazoxide (30-300 μM) significantly reduced the frequency of the mIPSCs in a dose-dependent manner. However, diazoxide did not affect the average value and the distribution of the mIPSC amplitudes. Thus, this effect of diazoxide was pre-synaptic in nature. The K(ATP) channel blocker glibenclamide (300 μM) was able to restore the frequency of the mIPSCs. These data suggest that the striatonigral projection, which represents the major inhibitory input controlling SNR GABA neuron activities, possesses presynaptic K(ATP) channels on the nerve terminals. -