Guanosine diphosphate is required for activation of a glyburide, ATP and cromakalim-sensitive outward current in rat hippocampal neurones

Abstract

Voltage-dependent outward currents were examined in CA1 neurones by whole-cell recording in slices. Nine cells were recorded with the 'standard' internal solution (KMeSO4, HEPES, EGTA, CaCl2, and MgCl2) and held a potential (-54 +/- 3 mV) at which there was no significant outward current. Cromakalim (CROM, 100 microM) reduced both input conductance (GN) (by 14 +/- 4%) and outward currents, evoked over a wide range of potentials by brief depolarizing pulses: at -4.0 +/- 3.0 mV, currents diminished by 30 +/- 10%. When 1 mM GDP was added to the standard internal solution, there was a significant outward current at approximately -54 mV; and CROM greatly increased outward currents near -4.0 mV (by 99 +/- 26.4%, n = 10). The enhanced outward currents were reduced by CROM washout (in two cells) and by 10 microM glyburide (GLYB, in four cells). When six other cells were recorded with electrodes containing both ATP (5 mM) and GDP (1 mM), there was no net outward current at approximately -54 mV and CROM reduced outward currents (at approximately 0 mV, by 37.5 +/- 10.9%). We conclude that GDP in hippocampal neurones appears to activate an ATP- and GLYB-sensitive outward current, which is much potentiated by CROM.