Altered cardiac sarcoplasmic reticulum function of intact myocytes of rat ventricle during metabolic inhibition.

Abstract:

:Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca(2+) and the perforated patch-clamp technique to measure SR Ca(2+) content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca(2+) (sparks and waves of Ca(2+)-induced Ca(2+) release), increased SR Ca(2+) content (79.4+/-5.7 to 115.2+/-6.6 micromol/L cell volume [mean+/-SEM; P:<0.001]), and, after a wave of Ca(2+) release, slower reuptake of Ca(2+) into the SR (rate constant of fall of Ca(2+) reduced from 8.5+/-1.1 s(-)(1) in control to 5.2+/-0.4 s(-)(1) in metabolic inhibition [P:<0.01]). Inhibition of L-type Ca(2+) channels with Cd(2+) (100 micromol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca(2+) sparks. These results are evidence of inhibition of both Ca(2+) release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca(2+) content at the time of reduced frequency of spontaneous release of Ca(2+) shows that the dominant effect of metabolic inhibition is to inhibit release of Ca(2+) from the SR, allowing the accumulation of greater than normal amounts of Ca(2+). In the context of ischemia, this extra accumulation of Ca(2+) would present a risk of potentially arrhythmogenic, spontaneous release of Ca(2+) on reperfusion of the tissue.

journal_name

Circ Res

journal_title

Circulation research

authors

Overend CL,Eisner DA,O'Neill SC

doi

10.1161/01.res.88.2.181

subject

Has Abstract

pub_date

2001-02-02 00:00:00

pages

181-7

issue

2

eissn

0009-7330

issn

1524-4571

journal_volume

88

pub_type

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