Fractional sr ca release is regulated by trigger ca and sr ca
content in cardiac myocytes.
Bassani, Jos[acute]e W. M., Weilong Yuan, and Donald M. Bers.
Department of Physiology, Loyola University School of Medicine,
Maywood, IL 60153, USA
APStracts 2:0121C, 1995.
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. (Amer. J. Physiol. 265: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], perforated patch to measure Ca current (ICa),
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],
[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 ICa 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 0.05-0.8 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.
Received 8 November 1994; accepted in final form 15 February
1995.
APS Manuscript Number C663-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 March 1995.