Phenylephrine and ATP enhance an amiloride insensitive bicarbonate-dependent alkalinizing mechanism in rat single cardiomyocytes

André Terzic, Michel Pucéat, Odile Clément-Chomienne, Guy Vassort

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

To expel the excess protons generated during a cellular acidification and to fully recover basal intracellular pH (pHi), cardiac cells rely on the amiloride-sensitive Na/H antiport. We report that rat single ventricular cardiomyocytes, loaded with the fluorescent pH indicator Snarf-1 and treated with inhibitors of the Na/H antiport, amiloride or its analogues, partially restored their pHi through a bicarbonate-dependent mechanism following an acidosis (imposed by the ammonia-pulse technique). In the presence of ethylisopropylamiloride (10 μM) or amiloride (1 mM) and 25 mM bicarbonate in the extracellular solution, the average time that cells needed to recover half of their pHi, following the removal of 20 mM NH4Cl, was 3.4 min, while the rate of proton efflux was calculated to be 2.0 mM/min. The stilbene derivative, 4-4′-di-isothiocyanostilbene-2,2′-disulphonate (DIDS 200 μM), a known blocker of anion transporters, inhibited this recovery. Both phenylephrine (100 μM, 3 μM propranolol present), an al-adrenoceptor agonist, and ATP (10 μM), a purinergic agonist, significantly enhanced the rate of proton efflux that was due to this HC03-dependent alkalinizing mechanism. Phenylephrine and ATP also shortened by three-fold the time that a myocyte needed to recover half of its initial pHi. This bicarbonate-dependent alkalinizing mechanism could provide an additional means by which cardiac cells recover their pHi from acidosis, especially under conditions in which the Na/H antiport is inhibited. Furthermore, catecholamines and ATP, which are released under various pathophysiological conditions often associated with intracellular acidosis, could play an important role in the modulation of pHi under these conditions.

Original languageEnglish (US)
Pages (from-to)597-600
Number of pages4
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume346
Issue number5
DOIs
StatePublished - Nov 1992

Keywords

  • ATP
  • Bicarbonate-dependent transporter
  • Cardiomyocyte
  • Intracellular pH
  • α-adrenoceptor

ASJC Scopus subject areas

  • Pharmacology

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