Alpha 1‐adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells.

A. Terzic, M. Pucéat, O. Clément, F. Scamps, G. Vassort

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126 Scopus citations

Abstract

1. The cellular effects of alpha 1‐adrenoceptor stimulation by phenylephrine were studied in the presence of propranolol in single cells isolated from the ventricles of rat hearts. 2. Phenylephrine (10‐100 microM) induced a biphasic pattern of inotropism in these cells: a transient negative followed by a sustained positive inotropic effect as usually observed in cardiac tissues. 3. In Snarf‐1‐loaded cells, phenylephrine induced an alkalinization. This effect was reversible on wash‐out and inhibited by prazosin, an alpha 1‐adrenoceptor antagonist. 4. The alpha 1‐adrenoceptor‐mediated increase in intracellular pH (pHi) was 0.1 pH unit in HEPES buffer containing 4.4 mM‐NaHCO3 and in Krebs buffer containing 25 mM‐NaHCO3. 5. The alkalinization was blocked by the Na(+)‐H+ antiport blocker, ethylisopropylamiloride (EIPA). 6. The recovery from an acidosis induced by a NH4Cl pre‐pulse was accelerated by phenylephrine. The phenylephrine‐induced alkalinization was attributed to activation of the Na(+)‐H+ antiport. 7. Despite its ability to increase pHi, phenylephrine did not alter Ca2+ current amplitude and kinetics. 8. Ca2+ transients recorded in Indo‐1‐loaded cells were not augmented by phenylephrine. Diastolic calcium level was decreased. 9. In single skinned cells, the Ca2+ sensitivity of the contractile proteins was increased by a pre‐treatment with phenylephrine even when the alpha 1‐adrenoceptor‐mediated alkalinizing effect had been prevented by EIPA. 10. These results lead us to propose that the alpha 1‐adrenergic‐induced positive inotropic response of heart muscle could result from an increased sensitivity of the myofilaments to Ca2+ ions. This alpha 1‐adrenoceptor‐mediated Ca2+ sensitization could result both from an intracellular alkalinization and from a direct effect on contractile proteins.

Original languageEnglish (US)
Pages (from-to)275-292
Number of pages18
JournalThe Journal of Physiology
Volume447
Issue number1
DOIs
StatePublished - Feb 1 1992

ASJC Scopus subject areas

  • Physiology

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