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Actions of cromakalim on outward currents of CA1 neurones in hippocampal slices
Author(s) -
Erdemli G.,
Krnjevic K.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17004.x
Subject(s) - chemistry , reversal potential , electrophysiology , tetrodotoxin , depolarization , membrane potential , biophysics , medicine , endocrinology , patch clamp , biology
1 Membrane effects of cromakalim (Crom; 50–300 μ m ) 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°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 ± 66pA) or input conductance (G N ) (‐ 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 ( I DR ) type. 5 The Crom‐control difference current ( I Crom ) 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 ≥ − 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, Crom produced no consistent increases in G N ; 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 by Crom 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 μ m ), but much less consistently by glibenclamide (10–30 μ m ). 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.