Possible functional linkage between the cardiac dihydropyridine and ryanodine receptor: Acceleration of rest decay by Bay K 8644

E. McCall, L. V. Hryshko, V. M. Stiffel, D. M. Christensen, Donald M Bers

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal I(Ca) trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or I(Ca). To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).

Original languageEnglish (US)
Pages (from-to)79-93
Number of pages15
JournalJournal of Molecular and Cellular Cardiology
Volume28
Issue number1
DOIs
StatePublished - Jan 8 1996
Externally publishedYes

Fingerprint

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
L-Type Calcium Channels
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Ryanodine
Ferrets
Contracture
Muscle Cells
Caffeine
Action Potentials
Muscles

Keywords

  • Bay K 8644
  • Cardiac muscle
  • Dihydropyridine receptor
  • Ryanodine receptor
  • Sarcolemmal Ca channel
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Possible functional linkage between the cardiac dihydropyridine and ryanodine receptor : Acceleration of rest decay by Bay K 8644. / McCall, E.; Hryshko, L. V.; Stiffel, V. M.; Christensen, D. M.; Bers, Donald M.

In: Journal of Molecular and Cellular Cardiology, Vol. 28, No. 1, 08.01.1996, p. 79-93.

Research output: Contribution to journalArticle

@article{011b16c0deb445fcb9dc76b921922d49,
title = "Possible functional linkage between the cardiac dihydropyridine and ryanodine receptor: Acceleration of rest decay by Bay K 8644",
abstract = "The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal I(Ca) trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or I(Ca). To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).",
keywords = "Bay K 8644, Cardiac muscle, Dihydropyridine receptor, Ryanodine receptor, Sarcolemmal Ca channel, Sarcoplasmic reticulum",
author = "E. McCall and Hryshko, {L. V.} and Stiffel, {V. M.} and Christensen, {D. M.} and Bers, {Donald M}",
year = "1996",
month = "1",
day = "8",
doi = "10.1006/jmcc.1996.0008",
language = "English (US)",
volume = "28",
pages = "79--93",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Possible functional linkage between the cardiac dihydropyridine and ryanodine receptor

T2 - Acceleration of rest decay by Bay K 8644

AU - McCall, E.

AU - Hryshko, L. V.

AU - Stiffel, V. M.

AU - Christensen, D. M.

AU - Bers, Donald M

PY - 1996/1/8

Y1 - 1996/1/8

N2 - The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal I(Ca) trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or I(Ca). To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).

AB - The effect of the dihydropyridine L-Type Ca chanel agonist Bay K 8644 on post-rest contractions in ferret ventricular muscle and isolated myocytes was investigated. Bay K 8644 was shown to abolish rest potentiation and greatly accelerate rest decay. The post-rest contraction suppressed by Bay K 8644 was accompanied by action potentials of large amplitude and longer duration, but voltage-clamp measurements showed that this suppression was not due to a supra-optimal I(Ca) trigger. Caffeine-induced contractures and rapid cooling contractures demonstrated an accelerated rest-dependent decline in sarcoplasmic reticulum (SR) Ca content in the presence of Bay K 8644, which was present even with Ca-free superfusion during rest. Thus, the Bay K 8644-induced decline of SR Ca during rest was independent of extracellular Ca or I(Ca). To explore whether the binding of Bay K 8644 to the dihydropyridine receptor could alter the SR Ca release channel/ryanodine receptor in a more direct way, ryanodine binding was measured in the absence and presence of Bay K 8644. Ryanodine binding to isolated ferret ventricular myocytes was increased by Bay K 8644 under conditions where sarcolemmal-SR junctions might be expected to be intact, but not after physical disruption. These results are consistent with a working hypothesis where Bay K 8644 may bind to the dihydropyridine receptor and this may lead to physical changes in the linkage between the dihydropridine receptor and a subset of ryanodine receptors, thereby increasing the opening of the SR Ca release channel during rest (and accelerating resting Ca loss).

KW - Bay K 8644

KW - Cardiac muscle

KW - Dihydropyridine receptor

KW - Ryanodine receptor

KW - Sarcolemmal Ca channel

KW - Sarcoplasmic reticulum

UR - http://www.scopus.com/inward/record.url?scp=0029985284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029985284&partnerID=8YFLogxK

U2 - 10.1006/jmcc.1996.0008

DO - 10.1006/jmcc.1996.0008

M3 - Article

C2 - 8745216

AN - SCOPUS:0029985284

VL - 28

SP - 79

EP - 93

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 1

ER -