Actions of cromakalim on outward currents of CA1 neurones in hippocampal slices.

1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic acid and (in most cases) bicuculline, bath applied Crom produced no consistent change in holding current (-59 +/- 66 pA) or input conductance (GN) (-3.9 +/- 5.2%). 3. Overall there were no significant changes in instantaneous inward rectification or in Q-current inward relaxations. 4. In 18 out of 22 cells, outward currents, evoked by 0.5 s pulses to voltages > -50 and < -20 mV, were depressed by Crom (by 42 +/- 11%, for n = 22). Because this effect was consistently seen in Ca current-blocking media, containing either Mn and low Ca, or Cd (and also carbachol), the K channels depressed by Crom were probably of the delayed rectifier (IDR) type. 5. The Crom-control difference current (ICrom), obtained with slow depolarizing ramps, had a biphasic character, inward in the voltage (V) range > -50 < -20 mV (where outward currents are depressed by Crom) and tending outward for V > or = -20 mV. 6. In 10 out of 11 cells, Crom potentiated a D-like, slowly-inactivating outward current (by 88 +/- 31%, for n = 11). 7 The effects of Crom and of 2 min periods of anoxia were compared in 12 cells: unlike anoxia, Cromproduced no consistent increases in GN; the currents evoked in the same cells by anoxia differed significantly from those evoked by Crom (by 150 +/- 60 pA); the directions of current changes induced byCrom and anoxia respectively were not significantly correlated. Crom strongly depressed anoxic outward currents (by 80 +/- 12%, n = 4).8 Some Crom-induced effects (increases in D-like current and the outward current elicited at V>- 20 mV) were always reversed by tolbutamide (1 mM), but much less consistently by glibenclamide(10-30 microM).9 In conclusion, the effects of Crom, recorded with intracellular electrodes in CA1 neurones in slices,show little resemblance to the effects of activation of ATP-sensitive K channels.