Reduction of spike frequency adaptation and blockade of M-current in rat CA1 pyramidal neurones by linopirdine (DuP 996), a neurotransmitter release enhancer
| Autor: | S P, Aiken, B J, Lampe, P A, Murphy, B S, Brown |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Indoles Pyridines Spike train Action Potentials Hippocampal formation Linopirdine chemistry.chemical_compound M current medicine Potassium Channel Blockers Animals Neurotransmitter Pharmacology Membrane potential Neurotransmitter Agents Pyramidal Cells Depolarization Adaptation Physiological Rats Electrophysiology chemistry Neuroscience Ion Channel Gating medicine.drug Research Article |
| Zdroj: | British journal of pharmacology. 115(7) |
| ISSN: | 0007-1188 |
| Popis: | 1. Linopirdine (DuP 996) has been shown to enhance depolarization-induced release of several neurotransmitters in the CNS through a mechanism which may involve K+ channel blockade. The electrophysiological effects of linopirdine were therefore investigated directly, by use of conventional voltage recording and single electrode voltage-clamp. 2. Linopirdine (10 microM) reduced spike frequency adaptation (SFA) in rat hippocampal CA1 pyramidal neurones in vitro. The reduction of SFA comprised an increase in number of spikes and a reduction in inter-spike intervals after the first, but with no effect on time to first spike. Linopirdine also caused a voltage-dependent depolarization of resting membrane potential (RMP). 3. M-current (IM), a current known to underlie SFA and to set RMP, was blocked by linopirdine in a reversible, concentration-dependent manner (IC50 = 8.5 microM). This block was not reversed by atropine (10 microM). 4. Linopirdine did not affect IQ, the slow after-hyperpolarization following a spike train, or spike duration. 5. Linopirdine may represent a novel class of K+ blocker with relative selectivity for the M-current. This block of IM is consistent with the suggestion from a previous study that linopirdine may affect a tetraethylammonium-sensitive channel, and it could be speculated that IM blockade may be involved with the enhancement of neurotransmitter release by linopirdine. |
| Databáze: | OpenAIRE |
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