Partial inhibition of sarcoplasmic reticulum Ca release evokes long-lasting Ca release events in ventricular myocytes: Role of luminal Ca in termination of Ca release

Aleksey V. Zima, Eckard Picht, Donald M Bers, Lothar A. Blatter

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

In cardiac myocytes, local sarcoplasmic reticulum (SR) Ca depletion during Ca sparks is believed to play an important role in the termination of SR Ca release. We tested whether decreasing the rate of SR Ca depletion by partially inhibiting SR Ca release channels (ryanodine receptors) delays Ca spark termination. In permeabilized cat ventricular myocytes, 0.7 mM tetracaine caused almost complete Ca spark inhibition followed by a recovery significantly below control level. The recovery was associated with increased SR Ca load and increased Ca spark duration. Additionally, SR Ca release events lasting several hundred milliseconds occurred consistently. These events had a significantly lower initial Ca release flux followed by a stable plateau, indicating delayed release termination and maintained SR Ca load. Increasing SR Ca load (without inhibiting SR Ca release rate) or decreasing SR Ca release rate (without increasing SR Ca load) both induced only a small increase in spark duration. These results show that the combination of decreased release flux and increased SR Ca load has synergistic effects and exerts major changes on the termination of Ca release events. Long-lasting Ca release events may originate from highly interconnected release junctions where Ca diffusion from neighboring sites partially compensates Ca depletion, thereby delaying SR Ca-dependent termination. Eventually, these events terminate by luminal Ca-independent mechanisms, such as inactivation, adaptation, or stochastic attrition.

Original languageEnglish (US)
Pages (from-to)1867-1879
Number of pages13
JournalBiophysical Journal
Volume94
Issue number5
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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