α1-Adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells

Andre Terzic, M. Puceat, O. Clement, F. Scamps, G. Vassort

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

1. The cellular effects of α1-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 μM) 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 α1-adrenoceptor antagonist. 4. The α1-adrenoceptor-mediated increase in intracellular pH (pH(i)) 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 pH(i), 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 α1-adrenoceptor-mediated alkalinizing effect had been prevented by EIPA. 10. These results lead us to propose that the α1 adrenergic-induced positive inotropic response of heart muscle could result from an increased sensitivity of the myofilaments to Ca2+ ions. This α1-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
JournalJournal of Physiology
Volume447
StatePublished - 1992
Externally publishedYes

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Myofibrils
Phenylephrine
Adrenergic Agents
Calcium
Adrenergic Receptors
Contractile Proteins
Ion Transport
Buffers
HEPES
Prazosin
Muscle Contraction
Acidosis
Propranolol
Heart Ventricles
Pulse
Myocardium
Ions

ASJC Scopus subject areas

  • Physiology

Cite this

α1-Adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells. / Terzic, Andre; Puceat, M.; Clement, O.; Scamps, F.; Vassort, G.

In: Journal of Physiology, Vol. 447, 1992, p. 275-292.

Research output: Contribution to journalArticle

Terzic, Andre ; Puceat, M. ; Clement, O. ; Scamps, F. ; Vassort, G. / α1-Adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells. In: Journal of Physiology. 1992 ; Vol. 447. pp. 275-292.
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