Premium
Reduction of spike frequency adaptation and blockade of M‐current in rat CA1 pyramidal neurones by linopirdine (DuP 996), a neurotransmitter release enhancer
Author(s) -
Aiken Simon P.,
Lampe Betty J.,
Brown Barry S.
Publication year - 1995
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.1476-5381.1995.tb15019.x
Subject(s) - depolarization , electrophysiology , membrane potential , chemistry , hyperpolarization (physics) , inhibitory postsynaptic potential , afterhyperpolarization , neuroscience , biophysics , voltage clamp , neurotransmitter , pharmacology , medicine , biology , central nervous system , organic chemistry , nuclear magnetic resonance spectroscopy
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 μ m ) 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 ( I M ), a current known to underlie SFA and to set RMP, was blocked by linopirdine in a reversible, concentration‐dependent manner (IC 50 = 8.5 μ m ). This block was not reversed by atropine (10 μ m ). 4 Linopirdine did not affect I Q , 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 I M is consistent with the suggestion from a previous study that linopirdine may affect a tetraethylammonium‐sensitive channel, and it could be speculated that I M blockade may be involved with the enhancement of neurotransmitter release by linopirdine.