Reduction of Spike Frequency Adaptation and Blockade of M-current in Rat CA1 Pyramidal Neurones by Linopirdine (DuP 996), a Neurotransmitter Release Enhancer

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1995 Aug 1

PMID 7582539

Citations 83

Authors

S P Aiken

B J Lampe

P A Murphy

B S Brown

Affiliations

Soon will be listed here.

Abstract

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.

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References

Pfaffinger P, Leibowitz M, Subers E, Nathanson N, Almers W, Hille B . Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. Neuron. 1988; 1(6):477-84. DOI: 10.1016/0896-6273(88)90178-x. View

Brown D, Marrion N, Smart T . On the transduction mechanism for muscarine-induced inhibition of M-current in cultured rat sympathetic neurones. J Physiol. 1989; 413:469-88. PMC: 1189111. DOI: 10.1113/jphysiol.1989.sp017664. View

Schafer S, Behe P, MEVES H . Inhibition of the M current in NG 108-15 neuroblastoma x glioma hybrid cells. Pflugers Arch. 1991; 418(6):581-91. DOI: 10.1007/BF00370575. View

Vickroy T . Presynaptic cholinergic actions by the putative cognitive enhancing agent DuP 996. J Pharmacol Exp Ther. 1993; 264(2):910-7. View

Stansfeld C, Marsh S, Gibb A, Brown D . Identification of M-channels in outside-out patches excised from sympathetic ganglion cells. Neuron. 1993; 10(4):639-54. DOI: 10.1016/0896-6273(93)90166-o. View

Warman E, Durand D, Yuen G . Reconstruction of hippocampal CA1 pyramidal cell electrophysiology by computer simulation. J Neurophysiol. 1994; 71(6):2033-45. DOI: 10.1152/jn.1994.71.6.2033. View

Brown D, Adams P, Constanti A . Voltage-sensitive K-currents in sympathetic neurons and their modulation by neurotransmitters. J Auton Nerv Syst. 1982; 6(1):23-35. DOI: 10.1016/0165-1838(82)90019-4. View

Brown D, Adams P . Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature. 1980; 283(5748):673-6. DOI: 10.1038/283673a0. View

Maciag C, Logue A, Tinker W, Saydoff J, Tam S, Zaczek R . Studies on the role of K+, Cl- and Na+ ion permeabilities in the acetylcholine release enhancing effects of linopirdine (DuP 996) in rat cortical slices. J Pharmacol Exp Ther. 1994; 271(2):891-7. View

10.

Benardo L, Prince D . Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells. Brain Res. 1982; 249(2):333-44. DOI: 10.1016/0006-8993(82)90067-1. View

11.

Halliwell J, Adams P . Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 1982; 250(1):71-92. DOI: 10.1016/0006-8993(82)90954-4. View

12.

Madison D, Nicoll R . Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. J Physiol. 1984; 354:319-31. PMC: 1193414. DOI: 10.1113/jphysiol.1984.sp015378. View

13.

Nakajima Y, Nakajima S, Leonard R, Yamaguchi K . Acetylcholine raises excitability by inhibiting the fast transient potassium current in cultured hippocampal neurons. Proc Natl Acad Sci U S A. 1986; 83(9):3022-6. PMC: 323439. DOI: 10.1073/pnas.83.9.3022. View

14.

Lancaster B, Adams P . Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. J Neurophysiol. 1986; 55(6):1268-82. DOI: 10.1152/jn.1986.55.6.1268. View

15.

Lancaster B, Nicoll R . Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J Physiol. 1987; 389:187-203. PMC: 1192077. DOI: 10.1113/jphysiol.1987.sp016653. View

16.

Dutar P, Nicoll R . Classification of muscarinic responses in hippocampus in terms of receptor subtypes and second-messenger systems: electrophysiological studies in vitro. J Neurosci. 1988; 8(11):4214-24. PMC: 6569473. View

17.

Storm J . Temporal integration by a slowly inactivating K+ current in hippocampal neurons. Nature. 1988; 336(6197):379-81. DOI: 10.1038/336379a0. View

18.

Brown D . M-currents: an update. Trends Neurosci. 1988; 11(7):294-9. DOI: 10.1016/0166-2236(88)90089-6. View

19.

Benson D, Blitzer R, Landau E . An analysis of the depolarization produced in guinea-pig hippocampus by cholinergic receptor stimulation. J Physiol. 1988; 404:479-96. PMC: 1190837. DOI: 10.1113/jphysiol.1988.sp017301. View

20.

Storm J . An after-hyperpolarization of medium duration in rat hippocampal pyramidal cells. J Physiol. 1989; 409:171-90. PMC: 1190438. DOI: 10.1113/jphysiol.1989.sp017491. View