Opposing effects of α1-adrenergic receptor subtypes on Ca2+ and pH homeostasis in rat cardiac myocytes

Giovanni Gambassi, Harold A. Spurgeon, Bruce D. Ziman, Edward G. Lakatta, Maurizio C. Capogrossi

Research output: Contribution to journalArticle

Abstract

We examined the effect of α1-adrenergic receptor (AR) subtypes on contraction, cytosolic Ca2+ concentration ([Ca2+](i)), and cytosolic pH (pH(i)) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxyseminaphthorhodafluor-1. Nonselective α1-AR stimulation was effected with phenylephrine plus nadolol. α1-AR subtype stimulation was achieved with α1-AR and chloroethylclonidine (CEC) or with α1-AR and WB-4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically stimulated at 0.5 Hz. Results show that 1) nonselective α1-AR stimulation increased twitch and [Ca2+](i) transient amplitudes, myofilament response to Ca2+ via cytosolic alkalinization; 3) α1-AR plus WB-4101 decreased twitch and [Ca2+](i) transient amplitudes and also pH(i); and 4) cytosolic acidification due to α1-AR plus WB-4101 was abolished by protein kinase C inhibition (staurosporine pretreatment) or downregulation (prolonged exposure to phorbol esters). In summary, the net effects of α1- adrenergic stimulation on contraction, [Ca2+](i) and pH(i) are due to opposing WB-4101- and CEC-sensitive α1-AR subtype signaling pathways.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume274
Issue number4 43-4
Publication statusPublished - Apr 1998

Keywords

  • α-adrenoceptor subtypes
  • Cardiac inotropy
  • Chloroethylclonidine
  • Cytosolic pH
  • Indo 1
  • WB-4101

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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