Actions of diazoxide on CA1 neurons in hippoeampal slices from rats

Abstract

Membrane effects of diazoxide (DZX) were examined in CA1 pyramidal neurons, mainly by whole-cell recording in slices kept at 33 °C (from Sprague–Dawley rats). Bath applications of DZX (0.65 mM) did not significantly change the resting input conductance; but instantaneous inward rectification was reduced by 47 ± 14% (near –110 mV). There was a similar depression of a large, sustained voltage-dependent outward current (by 44 ± 11% near 0 mV). A nearly identical reduction of the outward current recorded in a Ca current suppressing medium (but not in 30 mM tetraethylammonium) indicated that the DZX-sensitive current includes the delayed rectifier. In Mn, low-Ca medium containing tetraethylammonium and carbachol, DZX potentiated (by 43 ± 12%) the D-type slowly decaying outward current seen after hyperpolarizing pulses at a holding potential of ≈ −50 mV. DZX abolished or depressed slow inward currents, such as the tetrodotoxin-sensitive persistent Na current, high voltage activated Ca currents (IC50 = 0.47 mM), and the Q current. In 6 of 13 cells recorded with electrodes containing either guanosine or adenosine diphosphate, DZX potentiated the voitage-dependent outward current, but input conductances were reduced. In conclusion, although there was little indication that it activates classical KATP channels in CA1 neurons, DZX strongly depresses several voltage-dependent, slowly inactivating outward and inward currents, which are important modulators of cell excitability.Key words: KATP channels, persistent Na current, high voltage activated Ca currents, delayed rectifier, D current, sulphonylureas, nucleotide diphosphates.