Intracellular [Na+] and Na+ pump rate in rat and rabbit ventricular myocytes

Sanda Despa, Mohammed A. Islam, Steven M. Pogwizd, Donald M Bers

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98 Citations (Scopus)

Abstract

Intracellular [Na+] [Na+]i) is centrally involved in regulation of cardiac Ca2+ and contractility via Na+-Ca2+ exchange (NCX) and Na+-H+ exchange (NHX). Previous work has indicated that [Na+]i is higher in rat than rabbit ventricular myocytes. This has major functional consequences, but the reason for the higher [Na+]i in rat is unknown. Here, resting [Na+]i was measured using the fluorescent indicator SBFI, with both traditional calibration and a novel null-point method (which circumvents many limitations of prior methods). In rabbit, resting [Na+]i was 4.5 ± 0.4 mM (traditional calibration) and 4.4 mM (null-point). Resting [Na+]i in rat was significantly higher using both the traditional calibration (11.1 ± 0.7 mM) and the null-point approach (11.2 mM). The rate of Na+ transport by the Na+ pump was measured as a function of [Na+]i in intact cells. Rat cells exhibited a higher Vmax than rabbit (7.7 ± 1.1 vs. 4.0 ± 0.5 mm min-1) and a higher Km (10.2 ± 1.2 vs. 7.5 ± 1.1 mM). This results in little difference in pump activity for a given [Na+]i below 10 mM, but at measured resting [Na] i levels the pump-mediated Na+ efflux is much higher in rat. Thus, Na+ pump rate cannot explain the higher [Na+]i in rat. Resting Na+ influx rate was two to four times higher in rat, and this accounts for the higher resting [Na+]i. Using tetrodotoxin, HOE-642 and Ni2+ to block Na+ channels, NHX and NCX, respectively, we found that all three pathways may contribute to the higher resting Na+ influx in rat (albeit differentially). We conclude that resting [Na+]i is higher in rat than in rabbit, that this is caused by higher resting Na+ influx in rat and that a higher Na+,K+-ATPase pumping rate in rat is a consequence of the higher [Na+]i.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalJournal of Physiology
Volume539
Issue number1
DOIs
StatePublished - Feb 15 2002
Externally publishedYes

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Muscle Cells
Rabbits
Calibration
Tetrodotoxin

ASJC Scopus subject areas

  • Physiology

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Intracellular [Na+] and Na+ pump rate in rat and rabbit ventricular myocytes. / Despa, Sanda; Islam, Mohammed A.; Pogwizd, Steven M.; Bers, Donald M.

In: Journal of Physiology, Vol. 539, No. 1, 15.02.2002, p. 133-143.

Research output: Contribution to journalArticle

Despa, Sanda ; Islam, Mohammed A. ; Pogwizd, Steven M. ; Bers, Donald M. / Intracellular [Na+] and Na+ pump rate in rat and rabbit ventricular myocytes. In: Journal of Physiology. 2002 ; Vol. 539, No. 1. pp. 133-143.
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