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

doi:10.1016/0896-6273(88)90178-X

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 journal › Article › peer-review

91 Scopus citations

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 language	English (US)
Pages (from-to)	477-484
Number of pages	8
Journal	Neuron
Volume	1
Issue number	6
DOIs	https://doi.org/10.1016/0896-6273(88)90178-X
State	Published - Aug 1988
Externally published	Yes

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/0896-6273(88)90178-X

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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",

note = "Funding Information: We thank Lea Miller and Don G. Anderson for assistance. This work was supported by National Institutes of Health grants NS08174, AR17803, and HL30639 and training grant CM07270. M. D. L. is an FESN scholar in “transduction of neuronal signals.” N. M. N. is an Established Investigator of the American Heart Association.",

year = "1988",

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doi = "10.1016/0896-6273(88)90178-X",

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AU - Pfaffinger, Paul J.

AU - Leibowitz, Mark D.

AU - Subers, Emily M.

AU - Nathanson, Neil M.

AU - Almers, Wolfhard

AU - Hille, Bertil

N1 - Funding Information: We thank Lea Miller and Don G. Anderson for assistance. This work was supported by National Institutes of Health grants NS08174, AR17803, and HL30639 and training grant CM07270. M. D. L. is an FESN scholar in “transduction of neuronal signals.” N. M. N. is an Established Investigator of the American Heart Association.

PY - 1988/8

Y1 - 1988/8

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.

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

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