Depolarization of cardiac membrane potential synchronizes calcium sparks and waves in tissue

Daisuke Sato, Daniel C. Bartos, Kenneth S Ginsburg, Donald M Bers

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The diastolic membrane potential (Vm) can be hyperpolarized or depolarized by various factors such as hyperkalemia or hypokalemia in the long term, or by delayed afterdepolarizations in the short term. In this study,weinvestigate how Vm affects Ca sparks and waves. We use a physiologically detailed mathematical model to investigate individual factors that affect Ca spark generation and wave propagation.We focus on the voltage range of -90 ̃ -70 mV, which is just below the Vm for sodium channel activation. We find that Vm depolarization promotes Ca wave propagation and hyperpolarization prevents it. This finding is directly validated in voltage clamp experiments with Ca waves using isolated rat ventricular myocytes. Ca transport by the sodium-calcium exchanger (NCX) is determined by Vm as well as Na and Ca concen trations. Depolarized Vm reduces NCX-mediated efflux, elevating [Ca]i, and thus promoting Ca wave propagation. Moreover, depolarized Vm promotes spontaneous Ca releases that can cause initiation of multiple Ca waves. This indicates that during delayed afterdepolarizations, Ca release units (CRUs) interact with not just the immediately adjacent CRUs via Ca diffusion, but also further CRUs via fast (∼0.1 ms) changes in Vm mediated by the voltage and Ca-sensitive NCX. This may contribute significantly to synchronization of Ca waves among multiple cells in tissue.

Original languageEnglish (US)
Pages (from-to)1313-1317
Number of pages5
JournalBiophysical Journal
Volume107
Issue number6
DOIs
StatePublished - Sep 16 2014

ASJC Scopus subject areas

  • Biophysics

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