Inotropic and lusitropic effects induced by the inhibitory factor of the Na/Ca exchanger are not mediated by the β-adrenergic activation

Beni Shpak, Chagit Shpak, Reuben Hiller, Liron Boyman, Daniel Khananshvili*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Recently, an endogenous inhibitory factor (NCXIF) of the cardiac Na/Ca exchanger (NCX1) has been isolated, purified, and preliminary characterized. Here, we demonstrate that low doses of NCXIF (10-7-10-8 M) induce strong inotropic effects in the guinea and rat ventricle strips, while having no detectable effects in the atria even at 10-5 M. The inotropic effects of NCXIF are species-specific; the rat ventricle muscle is 20 to 50 times more sensitive to varying doses of NCX IF than the guinea pig. On the other hand the extent of maximal inotropic response is more prominent in the guinea pig model (up to 6-fold enhancement) than in the rat (up to 2-fold enhancement). The NCXIF accelerates the single-twitch relaxation (lusitropic effect) in dose-dependent manner, reaching ∼2-fold shortening of twitch width at saturating doses. The dose-dependence curves of lusitropic and inotropic effects exhibit a reciprocal relationship, meaning that these two effects might share common mechanisms. To test a possible involvement of catecholamines, the effects of NCXIF were examined in the presence or absence of β-adrenergic blocker, deralin. The saturating doses of deralin (1-3 μM) do not alter either the NCX IF-induced acceleration of relaxation or twitch enhancement, meaning that the NCXIF effects cannot be mediated by occasional release of endogenous catecholamines. The capacity of NCXIF to modulate the ventricle contractility unconnectedly to the β-adrenergic activation may provide new rational clues for future pharmacological interventions.

Original languageEnglish
Pages (from-to)466-472
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume44
Issue number4
DOIs
StatePublished - Oct 2004

Keywords

  • Endogenous inhibitor
  • Inotropy
  • Lusitropy
  • NCX 1
  • Na-Ca exchanger

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