κ-Opioid peptide receptor stimulation increases cytosolic pH and myofilament responsiveness to Ca2+ in cardiac myocytes

C. Ventura, M. C. Capogrossi, H. A. Spurgeon, E. G. Lakatta

Research output: Contribution to journalArticle

Abstract

Although κ- and δ-opioid receptors on mammalian cardiac myocytes have been discovered recently, the intracellular effects that result from stimulation of these receptors remain unknown. We examine the effects of a rapid and brief exposure to a κ-opioid receptor agonist on intracellular Ca2+, pH, and cell length in individual isolated rat ventricular cells. The specific κ-agonist trans-dl-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzene-acetamide (U-50488H) (methane sulfonate salt) caused a transient increase in cytosolic pH (pH(i)) measured from the change in SNARF-1 fluorescence and an increase in cytosolic [Ca2+] (Ca(i)), indexed by a change in indo-1 fluorescence. The initial Ca(i) increase often was followed by Ca(i) oscillations. Both pH(i) and Ca(i) effects were blocked by the specific antagonist κ-opioid receptor l-(N-furylmethyl)-α-normetazocine methane-sulfonate (Mr 1452). The amplitude of contraction that accompanied the Ca(i) increase elicited by U-50488H was greater than that associated with a similar increase in Ca(i) elicited by electrical stimulation or by the rapid exposure of cells to caffeine. Thus an acute and brief κ-opioid receptor stimulation of cardiac cells leads to an increase in Ca(i) and pH(i). The pH(i) increase was abolished by 1) blockade of the Na+-H+ exchanger by ethyl isopropyl amiloride and 2) inhibition of protein kinase C (PKC) activity via pretreatment with staurosporine or prolonged incubation with 4β-phorbol 12-myristate 13-acetate. These maneuvers did not abolish the U-50488H-induced increase in Ca(i). Thus the κ-opioid-induced increase in pH(i) and associated enhanced myofilament response to Ca2+ in individual heart cells likely is mediated, at least in part, via PKC activation of Na+-H+ exchange.

Original languageEnglish (US)
Pages (from-to)H1671-H1674
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume261
Issue number5 30-5
StatePublished - Dec 1 1991
Externally publishedYes

Keywords

  • Indo-1
  • SNARF-1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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