Sulphonylureas reduce the slowly inactivating D-type outward current in rat hippocampal neurons
| Autor: | Crépel, V, Krnjević, K, Ben-Ari, Y |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1993 |
| Předmět: |
Male
Neurons Potassium Channels Tolbutamide Electric Conductivity Tetraethylammonium Tetrodotoxin In Vitro Techniques Tetraethylammonium Compounds Hippocampus Membrane Potentials Rats Adenosine Triphosphate Sulfonylurea Compounds Glyburide Potassium Channel Blockers Animals Hypoglycemic Agents Rats Wistar Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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