Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression

Paul J. Pfaffinger, Mark D. Leibowitz, Emily M. Subers, Neil M. Nathanson, Wolfhard Almers, Bertil Hille

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([Ca2+]i), as determined with fura-2. Active phorhol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Cal+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.

Original languageEnglish (US)
Pages (from-to)477-484
Number of pages8
JournalNeuron
Volume1
Issue number6
DOIs
StatePublished - 1988
Externally publishedYes

Fingerprint

Type C Phospholipases
Phosphatidylinositols
Gonadotropin-Releasing Hormone
Inositol Phosphates
Fura-2
Phorbol Esters
Inositol
Substance P
Caffeine
Acetylcholine
Buffers
Esters

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. / Pfaffinger, Paul J.; Leibowitz, Mark D.; Subers, Emily M.; Nathanson, Neil M.; Almers, Wolfhard; Hille, Bertil.

In: Neuron, Vol. 1, No. 6, 1988, p. 477-484.

Research output: Contribution to journalArticle

Pfaffinger, Paul J. ; Leibowitz, Mark D. ; Subers, Emily M. ; Nathanson, Neil M. ; Almers, Wolfhard ; Hille, Bertil. / Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. In: Neuron. 1988 ; Vol. 1, No. 6. pp. 477-484.
@article{9c7b955e5f1449a38819f9efe2213d96,
title = "Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression",
abstract = "The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([Ca2+]i), as determined with fura-2. Active phorhol esters depressed M-current only 50{\%} and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Cal+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.",
author = "Pfaffinger, {Paul J.} and Leibowitz, {Mark D.} and Subers, {Emily M.} and Nathanson, {Neil M.} and Wolfhard Almers and Bertil Hille",
year = "1988",
doi = "10.1016/0896-6273(88)90178-X",
language = "English (US)",
volume = "1",
pages = "477--484",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression

AU - Pfaffinger, Paul J.

AU - Leibowitz, Mark D.

AU - Subers, Emily M.

AU - Nathanson, Neil M.

AU - Almers, Wolfhard

AU - Hille, Bertil

PY - 1988

Y1 - 1988

N2 - The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([Ca2+]i), as determined with fura-2. Active phorhol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Cal+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.

AB - The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([Ca2+]i), as determined with fura-2. Active phorhol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Cal+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.

UR - http://www.scopus.com/inward/record.url?scp=0024057849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024057849&partnerID=8YFLogxK

U2 - 10.1016/0896-6273(88)90178-X

DO - 10.1016/0896-6273(88)90178-X

M3 - Article

C2 - 2483099

AN - SCOPUS:0024057849

VL - 1

SP - 477

EP - 484

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 6

ER -