Sulphonylureas reduce the slowly inactivating D-type outward current in rat hippocampal neurons.

Abstract

1. Using intracellular recording in hippocampal slices, we have examined, in CA3 pyramidal neurons, the effects of sulphonylureas (blockers of ATP-sensitive K+ channels) on the slowly inactivating D-type K+ current (ID). 2. In the presence of TTX (1 microM) to block Na+ currents, ID had the following characteristics: activation by large depolarizing pulses from membrane potentials negative to -75 mV, slow inactivation kinetics, high sensitivity to 4-aminopyridine (4-AP, 3-40 microM), insensitivity to tetraethylammonium (TEA, 10 mM), Cs+ (3 mM) and carbachol (50 microM). 3. Applications of glibenclamide (10 microM) did not modify the input conductance of the cell, but reduced the amplitude of ID by 31.2 +/- 5.6% (n = 16), without altering its voltage dependence and inactivation kinetics. The effects were usually reversible. 4. Glibenclamide also reduced ID in the presence of TEA (10 mM), Cs+ (3 mM) and carbachol (50 microM), to block several K+ currents (IK, IC, IQ, IM), as well as kynurenate (1 mM) and bicuculline (10 microM) to block on-going synaptic currents mediated by activation of non-NMDA (N-methyl-D-aspartate) and GABA (gamma-aminobutyrate)-A receptors, respectively. 5. Comparable depressions of ID were produced by two other sulphonylureas: gliquidone (10 microM), 42.6 +/- 7.9% (n = 13) and tolbutamide (500 microM), 39.1 +/- 12.8 (n = 8). 6. It is concluded that, in the central nervous system, sulphonylureas can modulate K+ currents which are not generated by ATP-sensitive K+ channels.