Interactive α- and β-adrenergic actions of norepinephrine in rat cardiac myocytes

Robert S. Danziger, Makoto Sakai, Edward G. Lakatta, Richard G. Hansford

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the effects of the physiological neurotransmitter norepinephrine on the contractile properties and Ca2+ dynamics of isolated cardiac myocytes, with particular emphasis on possible interactions between α- and β-adrenergic effects. Individual rat ventricular myocytes were electrically stimulated at a frequency of 1 Hz. Norepinephrine (10-9 to 10-5 m) increased extent and velocity of shortening and decreased the contraction duration. β-Adrenergic activation gave a greater enhancement of extent and velocity of shortening than did norepinephrine alone (i.e. α plus β). Neither α1 nor α2 adrenergic activation individually produced a significant impact upon contraction. Using suspensions of myocytes loaded with Quin-2, we also studied resting levels of cytosolic Ca2+ ([Ca2+]c), the increase of [Ca2+]c due to caffeine-addition (as an index of sarcoplasmic reticulum Ca2+ content) and the subsequent increase in [Ca2+]c due to depolarization with 30 mm K+ (as an index of sarcolemmal voltage-dependent Ca2+ channel activity). Norepinephrine decreased resting [Ca2+]c, increased sarcoplasmic reticulum Ca2+ content and increased Ca2+ channel activity. β-Adrenergic activation produced the same effect on resting [Ca2+]c and sarcoplasmic reticulum content, but gave significantly greater activation of sarcolemmal Ca2+ channel activity, than did norepinephrine (α plus β). By contrast, α-adrenergic stimulation had no effect on resting [Ca2+]c or sarcoplasmic reticulum Ca2+ content. We conclude that β-mediated effects predominate in the action of the physiological agonist norepinephrine on cardiac myocytes. However, α (specifically α1)-adrenergic effects are significant in diminishing the potentiation of the extent and velocity of shortening, and of depolarization-induced entry of Ca2+ into the cell, which is seen on β-stimulation alone. Thus, there may be an intrinsic feedback effect in the actions of norepinephrine on the cardiac myocyte.

Original languageEnglish (US)
Pages (from-to)111-123
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume22
Issue number1
DOIs
StatePublished - Jan 1990
Externally publishedYes

Keywords

  • Autonomic modulation
  • Cardiac contractility
  • Cardiac myocytes
  • Cytosolic calcium
  • Receptor interactions

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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