Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes

J. W M Bassani, W. Yuan, Donald M Bers

Research output: Contribution to journalArticle

444 Citations (Scopus)

Abstract

The release of sarcoplasmic reticulum (SR) Ca in cardiac muscle during excitation-contraction coupling is known to be graded by the amount of activating Ca outside the SR (i.e., Ca-induced Ca release). However, little is known about how intra-SR Ca affects the release process. In this study we assessed how the fractional SR Ca release as described by Bassani et al. [Am. J. Physiol. 265 (Cell Physiol. 34): C533-C540, 1993] is affected by alteration of trigger Ca and of SR Ca content. Experiments were done with isolated ferret ventricular myocytes using indo 1 to measure Ca concentration, perforated patch to measure Ca current (I(Ca)), caffeine application to release SR Ca, and thapsigargin to completely block SR Ca uptake. For what we consider a Normal SR Ca load and trigger Ca [action potential at 0.5 Hz with 2 mM extracellular Ca concentration ([Ca](o))], 35 ± 3% of the SR Ca content was released at a twitch. Changing trigger Ca by altering [Ca](o) (to 0.5 and 8 mM) at a test twitch changed this fractional SR Ca release to 10 ± 2 and 59 ± 6%, with the same SR Ca load (and peak I(Ca) changed in a parallel manner in separate voltage-clamp experiments). Three different levels of SR Ca load were studied (Low, Normal, and High; by action potential stimulation at different frequencies from 0.05 to 0.8 Hz) using the same standard test trigger Ca (2 mM). Surprisingly, the High-load condition only increased SR Ca content by ~4% but appeared to be very close to the limiting SR Ca capacity. The fractional SR Ca release increased from 3.6 ± 0.8 to 35 ± 3 to 59 ± 8% for Low-, Normal-, and High-loading conditions. Thus a small increase in SR Ca content from the control value produced a large increase in fractional SR Ca release. This demonstrates a novel and important regulatory role of intra-SR Ca. This regulatory effect may be at least as quantitatively important as changes in trigger Ca in controlling the amount of Ca released and can also explain spontaneous SR Ca release during Ca overload.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume268
Issue number5 37-5
StatePublished - 1995
Externally publishedYes

Fingerprint

sarcoplasmic reticulum
Sarcoplasmic Reticulum
Cardiac Myocytes
Thapsigargin
Clamping devices
Caffeine
Muscle
Experiments
Electric potential
cardiomyocytes
action potentials
Action Potentials
indo-1
Excitation Contraction Coupling
Ferrets

Keywords

  • calcium
  • cardiac myocyte
  • ferret
  • fluorescence
  • sarcoplasmic reticulum
  • shortening

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes. / Bassani, J. W M; Yuan, W.; Bers, Donald M.

In: American Journal of Physiology - Cell Physiology, Vol. 268, No. 5 37-5, 1995.

Research output: Contribution to journalArticle

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title = "Fractional SR Ca release is regulated by trigger Ca and SR Ca content in cardiac myocytes",
abstract = "The release of sarcoplasmic reticulum (SR) Ca in cardiac muscle during excitation-contraction coupling is known to be graded by the amount of activating Ca outside the SR (i.e., Ca-induced Ca release). However, little is known about how intra-SR Ca affects the release process. In this study we assessed how the fractional SR Ca release as described by Bassani et al. [Am. J. Physiol. 265 (Cell Physiol. 34): C533-C540, 1993] is affected by alteration of trigger Ca and of SR Ca content. Experiments were done with isolated ferret ventricular myocytes using indo 1 to measure Ca concentration, perforated patch to measure Ca current (I(Ca)), caffeine application to release SR Ca, and thapsigargin to completely block SR Ca uptake. For what we consider a Normal SR Ca load and trigger Ca [action potential at 0.5 Hz with 2 mM extracellular Ca concentration ([Ca](o))], 35 ± 3{\%} of the SR Ca content was released at a twitch. Changing trigger Ca by altering [Ca](o) (to 0.5 and 8 mM) at a test twitch changed this fractional SR Ca release to 10 ± 2 and 59 ± 6{\%}, with the same SR Ca load (and peak I(Ca) changed in a parallel manner in separate voltage-clamp experiments). Three different levels of SR Ca load were studied (Low, Normal, and High; by action potential stimulation at different frequencies from 0.05 to 0.8 Hz) using the same standard test trigger Ca (2 mM). Surprisingly, the High-load condition only increased SR Ca content by ~4{\%} but appeared to be very close to the limiting SR Ca capacity. The fractional SR Ca release increased from 3.6 ± 0.8 to 35 ± 3 to 59 ± 8{\%} for Low-, Normal-, and High-loading conditions. Thus a small increase in SR Ca content from the control value produced a large increase in fractional SR Ca release. This demonstrates a novel and important regulatory role of intra-SR Ca. This regulatory effect may be at least as quantitatively important as changes in trigger Ca in controlling the amount of Ca released and can also explain spontaneous SR Ca release during Ca overload.",
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N2 - The release of sarcoplasmic reticulum (SR) Ca in cardiac muscle during excitation-contraction coupling is known to be graded by the amount of activating Ca outside the SR (i.e., Ca-induced Ca release). However, little is known about how intra-SR Ca affects the release process. In this study we assessed how the fractional SR Ca release as described by Bassani et al. [Am. J. Physiol. 265 (Cell Physiol. 34): C533-C540, 1993] is affected by alteration of trigger Ca and of SR Ca content. Experiments were done with isolated ferret ventricular myocytes using indo 1 to measure Ca concentration, perforated patch to measure Ca current (I(Ca)), caffeine application to release SR Ca, and thapsigargin to completely block SR Ca uptake. For what we consider a Normal SR Ca load and trigger Ca [action potential at 0.5 Hz with 2 mM extracellular Ca concentration ([Ca](o))], 35 ± 3% of the SR Ca content was released at a twitch. Changing trigger Ca by altering [Ca](o) (to 0.5 and 8 mM) at a test twitch changed this fractional SR Ca release to 10 ± 2 and 59 ± 6%, with the same SR Ca load (and peak I(Ca) changed in a parallel manner in separate voltage-clamp experiments). Three different levels of SR Ca load were studied (Low, Normal, and High; by action potential stimulation at different frequencies from 0.05 to 0.8 Hz) using the same standard test trigger Ca (2 mM). Surprisingly, the High-load condition only increased SR Ca content by ~4% but appeared to be very close to the limiting SR Ca capacity. The fractional SR Ca release increased from 3.6 ± 0.8 to 35 ± 3 to 59 ± 8% for Low-, Normal-, and High-loading conditions. Thus a small increase in SR Ca content from the control value produced a large increase in fractional SR Ca release. This demonstrates a novel and important regulatory role of intra-SR Ca. This regulatory effect may be at least as quantitatively important as changes in trigger Ca in controlling the amount of Ca released and can also explain spontaneous SR Ca release during Ca overload.

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