Opposing effects of alpha 1-adrenergic receptor subtypes on Ca2+ and pH homeostasis in rat cardiac myocytes

Giovanni Gambassi, 33183, DI MEDICINA E CHIRURGIA "A.GEMELLI" FACOLTA', ROMA - Dipartimento di Medicina e chirurgia traslazionale, Ha Spurgeon, Bd Ziman, Eg Lakatta, Mc Capogrossi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

We examined the effect of alpha 1-adrenergic receptor (AR) subtypes on contraction, cytosolic Ca2+ concentration ([Ca2+]i), and cytosolic pH (pHi) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxyseminaphthorhodafluor-1. Nonselective alpha 1-AR stimulation was effected with phenylephrine plus nadolol. alpha 1-AR subtype stimulation was achieved with alpha 1-AR and chloroethylclonidine (CEC) or with alpha 1-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 alpha 1-AR stimulation increased twitch and [Ca2+]i transient amplitudes, myofilament response to Ca2+, and pHi; 2) alpha 1-AR plus CEC increased twitch and [Ca2+]i transient amplitudes and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3) alpha 1-AR plus WB-4101 decreased twitch and [Ca2+]i transient amplitudes and also pHi; and 4) cytosolic acidification due to alpha 1-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 alpha 1-adrenergic stimulation on contraction, [Ca2+]i, and pHi are due to opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways.
Lingua originaleEnglish
pagine (da-a)H1152-H1152-62
RivistaAMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY
Volume274
Stato di pubblicazionePubblicato - 1998

Keywords

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Animals
  • Calcium
  • Clonidine
  • Dioxanes
  • Drug Combinations
  • Drug Synergism
  • Fluorescent Dyes
  • Homeostasis
  • Hydrogen
  • Hydrogen-Ion Concentration
  • Indoles
  • Male
  • Myocardial Contraction
  • Myocardium
  • Phenylephrine
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1

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