Acidosis masks β-adrenergic control of cardiac L-type calcium current

George J. Rozanski, Richard C. Witt

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The β-adrenergic control of the L-type Ca2* current (Ica) was examined as a function of extracellular pH (pHo) in guinea-pig ventricular myocytes using the wholecell voltage-clamp technique. ICa was elicited in Cs+-loaded myocytes by depolarizing pulses from a holding potential of -40 mV. The maximum ICa density in response to 0.01 or 1 μM isoproterenol was significantly less in myocytes pretreated with acidic external solution (pH 6.6 or 5.8) compared with cells studied at control pHo 7.4. This acidosis-induced decrease in β-responsiveness was also accompanied by a similar reduction in basal current density. Myocytes studied tinder alkaline conditions (pHo 8.2) also had reduced β-responsiveness although basal ICa density tended to be greater than control. In addition to the diminished effects of isoproterenol, acidic myocytes had smaller responses to extracellular forskolin and internally applied adenosine 3′.5′-cyclic mononophosphate. compared with control. The blunted responses to these latter stimuli were similar in magnitude to that observed with 1 μM isoproterenol. These findings suggest that protons interfere with the β-adrenergic control of ICa primarily by a direct inhibition of the Ca2+ channel which independently masks the effects of the adenylyl cyclase cascade.

Original languageEnglish (US)
Pages (from-to)1781-1788
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number9
DOIs
StatePublished - Sep 1995

Keywords

  • Acidosis
  • Calcium current
  • Forskolin
  • Isoproterenol
  • cyclic AMP

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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