Mechanisms of denervation supersensitivity in regionally denervated canine hearts

M. R. Warner, P. L. Wisler, T. D. Hodges, A. M. Watanabe, D. P. Zipes

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Abstract

Mechanisms responsible for 'denervation supersensitivity' in regionally denervated canine hearts were examined by measuring β-adrenergic receptor density and affinity and the density of the α-subunit of the stimulatory G protein (G(s)α). Sympathetic denervation was produced by applying an epicardial strip of phenol midway between the left ventricular (LV) base and apex. Six to eight days after denervation, dogs were anesthetized and then underwent functional studies (n = 4) or hearts were excised for biochemical analyses (n = 6). Biochemical studies were also done on 3 nondenervated hearts. Effective refractory periods (ERPs) were measured in innervated (base) and denervated (apex) LV myocardium. During sympathetic stimulation (2 and 4 Hz), the ERP shortened more (P < 0.05) at basal than at apical sites, whereas during norepinephrine infusion (0.05 to 0.5 ug · kg-1 · min- 1), the ERP shortened more (P < 0.001) at apical than at basal sites. In regionally denervated hearts, however, the density and affinity of β- adrenergic receptors did not differ significantly (P > 0.2) in nondenervated basal compared with denervated apical myocardium. Quantitative immunoblotting of the G(s)α demonstrated that the density of the 47- and 52-kDa subunits was also similar (P > 0.6) in basal compared with apical myocardium from regionally denervated hearts. In addition, β-adrenergic receptor density and affinity and G(s)α density did not differ significantly (P > 0.5) in basal compared with apical myocardium from nondenervated control hearts. We conclude that denervation super sensitivity in regionally denervated canine hearts occurs independently of an increase in β-adrenergic receptor density or affinity or of a change in density of the 47- or 52-kDa G(s)α. These data suggest that an alteration distal to the β-adrenergic receptor, but not involving an increase in the density of G(s)α, potentiates adrenergic signal transduction in denervated areas of regionally denervated canine hearts.

Original languageEnglish (US)
Pages (from-to)H815-H820
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number3 33-3
StatePublished - Jan 1 1993

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Keywords

  • β-adrenergic receptors
  • G proteins
  • norepinephrine
  • sympathetic nerves

ASJC Scopus subject areas

  • Physiology

Cite this

Warner, M. R., Wisler, P. L., Hodges, T. D., Watanabe, A. M., & Zipes, D. P. (1993). Mechanisms of denervation supersensitivity in regionally denervated canine hearts. American Journal of Physiology - Heart and Circulatory Physiology, 264(3 33-3), H815-H820.