BAY K 8644 depresses excitation-contraction coupling in cardiac muscle

E. Mccall, Donald M Bers

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We determined the effect of the dihydropyridine L-type Ca channel agonist BAY K 8644 (BAY) on excitation-contraction (E-C) coupling in isolated ferret ventricular myocytes using whole cell voltage clamp. The sarcoplasmic reticulum (SR) Ca load during the test pulses, assessed by caffeine-induced contractures, was similar in the presence and absence of BAY, with extracellular Ca concentration lowered from 3 to 1 mM in BAY. The relationship between L-type Ca current (I(Ca)) and contraction was assessed, with current and contractions measured during depolarizations from -40 to between -30 and +50 mV after a conditioning train (to ensure constant SR Ca load). BAY shifted the current-contraction relationship downward, such that, for a given I(Ca) and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the current-voltage relationship. We conclude that BAY decreases the efficacy of a given Ca current to induce SR Ca release during E-C coupling in ferret cardiac tissue (in contrast to the BAY-induced increase of resting SR Ca release). This may reflect an alteration in the state of the SR Ca release channel due to BAY binding to dihydropyridine receptors.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume270
Issue number3 39-3
StatePublished - Mar 1996
Externally publishedYes

Fingerprint

Excitation Contraction Coupling
Sarcoplasmic Reticulum
Muscle
Myocardium
Ferrets
L-Type Calcium Channels
Depolarization
Clamping devices
Electric potential
Contracture
Caffeine
Muscle Cells
Tissue

Keywords

  • calcium current
  • dihydropyridine
  • ferret ventricular myocytes
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

BAY K 8644 depresses excitation-contraction coupling in cardiac muscle. / Mccall, E.; Bers, Donald M.

In: American Journal of Physiology - Cell Physiology, Vol. 270, No. 3 39-3, 03.1996.

Research output: Contribution to journalArticle

@article{3ef925eea14e4192947bcb2bb27fa7d1,
title = "BAY K 8644 depresses excitation-contraction coupling in cardiac muscle",
abstract = "We determined the effect of the dihydropyridine L-type Ca channel agonist BAY K 8644 (BAY) on excitation-contraction (E-C) coupling in isolated ferret ventricular myocytes using whole cell voltage clamp. The sarcoplasmic reticulum (SR) Ca load during the test pulses, assessed by caffeine-induced contractures, was similar in the presence and absence of BAY, with extracellular Ca concentration lowered from 3 to 1 mM in BAY. The relationship between L-type Ca current (I(Ca)) and contraction was assessed, with current and contractions measured during depolarizations from -40 to between -30 and +50 mV after a conditioning train (to ensure constant SR Ca load). BAY shifted the current-contraction relationship downward, such that, for a given I(Ca) and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the current-voltage relationship. We conclude that BAY decreases the efficacy of a given Ca current to induce SR Ca release during E-C coupling in ferret cardiac tissue (in contrast to the BAY-induced increase of resting SR Ca release). This may reflect an alteration in the state of the SR Ca release channel due to BAY binding to dihydropyridine receptors.",
keywords = "calcium current, dihydropyridine, ferret ventricular myocytes, sarcoplasmic reticulum",
author = "E. Mccall and Bers, {Donald M}",
year = "1996",
month = "3",
language = "English (US)",
volume = "270",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3 39-3",

}

TY - JOUR

T1 - BAY K 8644 depresses excitation-contraction coupling in cardiac muscle

AU - Mccall, E.

AU - Bers, Donald M

PY - 1996/3

Y1 - 1996/3

N2 - We determined the effect of the dihydropyridine L-type Ca channel agonist BAY K 8644 (BAY) on excitation-contraction (E-C) coupling in isolated ferret ventricular myocytes using whole cell voltage clamp. The sarcoplasmic reticulum (SR) Ca load during the test pulses, assessed by caffeine-induced contractures, was similar in the presence and absence of BAY, with extracellular Ca concentration lowered from 3 to 1 mM in BAY. The relationship between L-type Ca current (I(Ca)) and contraction was assessed, with current and contractions measured during depolarizations from -40 to between -30 and +50 mV after a conditioning train (to ensure constant SR Ca load). BAY shifted the current-contraction relationship downward, such that, for a given I(Ca) and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the current-voltage relationship. We conclude that BAY decreases the efficacy of a given Ca current to induce SR Ca release during E-C coupling in ferret cardiac tissue (in contrast to the BAY-induced increase of resting SR Ca release). This may reflect an alteration in the state of the SR Ca release channel due to BAY binding to dihydropyridine receptors.

AB - We determined the effect of the dihydropyridine L-type Ca channel agonist BAY K 8644 (BAY) on excitation-contraction (E-C) coupling in isolated ferret ventricular myocytes using whole cell voltage clamp. The sarcoplasmic reticulum (SR) Ca load during the test pulses, assessed by caffeine-induced contractures, was similar in the presence and absence of BAY, with extracellular Ca concentration lowered from 3 to 1 mM in BAY. The relationship between L-type Ca current (I(Ca)) and contraction was assessed, with current and contractions measured during depolarizations from -40 to between -30 and +50 mV after a conditioning train (to ensure constant SR Ca load). BAY shifted the current-contraction relationship downward, such that, for a given I(Ca) and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the current-voltage relationship. We conclude that BAY decreases the efficacy of a given Ca current to induce SR Ca release during E-C coupling in ferret cardiac tissue (in contrast to the BAY-induced increase of resting SR Ca release). This may reflect an alteration in the state of the SR Ca release channel due to BAY binding to dihydropyridine receptors.

KW - calcium current

KW - dihydropyridine

KW - ferret ventricular myocytes

KW - sarcoplasmic reticulum

UR - http://www.scopus.com/inward/record.url?scp=0029874395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029874395&partnerID=8YFLogxK

M3 - Article

C2 - 8638669

AN - SCOPUS:0029874395

VL - 270

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3 39-3

ER -