Neuroleptics antagonize a calcium-activated potassium channel in airway smooth muscle

John D McCann; Michael J Welsh

doi:10.1085/jgp.89.2.339

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Neuroleptics antagonize a calcium-activated potassium channel in airway smooth muscle

Journal article

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Neuroleptics antagonize a calcium-activated potassium channel in airway smooth muscle

John D McCann and Michael J Welsh

The Journal of general physiology, Vol.89(2), pp.339-352

1987

DOI: 10.1085/jgp.89.2.339

PMID: 2435843

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Abstract

We examined the effect of neuroleptics on Ca-activated K channels from dog airway smooth muscle cells. Because these agents inhibit a variety of other Ca-mediated processes, it seemed possible that they might also inhibit Ca-activated K channels. In excised, inside-out patches, several neuroleptics potently and reversibly inhibited the K channel from the internal but not the external surface of the patch. Measurements of the effect on open probability and open- and closed-state durations support a simple kinetic model in which neuroleptics bind to and block the open channel. Inhibition by neuroleptics was moderately voltage dependent, with blockers less potent at hyperpolarizing voltages. The relationship between voltage and the dissociation constant for the blocker suggests that the binding site is one-third of the way across the channel's electrical field. Equilibrium dissociation constants for the drug-channel complex were: haloperidol, 1.0 +/- 0.1 microM; trifluoperazine, 1.4 +/- 0.1 microM; thioridazine, 2.4 +/- 0.1 microM; and chlorpromazine, 2.0 microM. This rank-order potency is different from their potency as calmodulin inhibitors, which suggests that neuroleptics bind to the channel rather than a calmodulin-channel complex.

Neuropharmacology

Psychopharmacology

Psychology. Psychoanalysis. Psychiatry

Pharmacology. Drug treatments

Biological and medical sciences

Medical sciences

Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)

Details

Title: Subtitle: Neuroleptics antagonize a calcium-activated potassium channel in airway smooth muscle
Creators: John D McCann - Univ. Iowa coll. medicine, dep. internal medicine, Iowa City IA 52242, United States
Michael J Welsh - Univ. Iowa coll. medicine, dep. internal medicine, Iowa City IA 52242, United States
Resource Type: Journal article
Publication Details: The Journal of general physiology, Vol.89(2), pp.339-352
DOI: 10.1085/jgp.89.2.339
PMID: 2435843
NLM abbreviation: J Gen Physiol
ISSN: 0022-1295
eISSN: 1540-7748
Publisher: Rockefeller University Press; New York, NY
Language: English
Date published: 1987
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984020716102771

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