alpha1-Adrenergic Receptor Stimulation Decreases Maximum Shortening Velocity of Skinned Single Ventricular Myocytes From Rats

alpha1-Adrenergic agonists have negative inotropic effects on mammalian myocardium under some conditions, and biochemical experiments measuring the Ca plus-activated actomyosin ATPase activity of myofibrillar preparations suggest that this may result from a decrease in cross-bridge cycling rate caus...

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Veröffentlicht in:Circulation research 1995-07, Vol.77 (1), p.114-120
Hauptverfasser: Strang, Kevin T, Moss, Richard L
Format: Artikel
Sprache:eng
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Zusammenfassung:alpha1-Adrenergic agonists have negative inotropic effects on mammalian myocardium under some conditions, and biochemical experiments measuring the Ca plus-activated actomyosin ATPase activity of myofibrillar preparations suggest that this may result from a decrease in cross-bridge cycling rate caused by phosphorylation of myofilament proteins. Experiments with intact ventricular preparations, however, have failed to demonstrate a mechanical manifestation of a decrease in cycling rate. The present study examined the effect of alpha1-adrenergic receptor stimulation on maximum shortening velocity in skinned single ventricular myocytes from rats. Enzymatically isolated myocytes were incubated with the beta-receptor antagonist propranolol in the presence or absence of the alpha1-adrenergic receptor agonist phenylephrine and were then rapidly skinned to preserve the phosphorylation state of myofilament proteins. The velocity of unloaded shortening (Vo) was determined by use of the slack-test method and compared between skinned control and phenylephrine-treated cells. The relationship between isometric tension and [Ca plus] was also assessed for each myocyte. Vo was significantly lower in the alpha1-adrenergic receptor agonist-treated cells than in the control cells, but there was no effect on Ca plus sensitivity of isometric tension. In addition, the myosin heavy chain isoform composition accounted for a significant amount of the variation in Vo within the treatment groups. On the basis of these and previous results we propose that alpha1-adrenergic receptor stimulation inhibits cross-bridge cycling rate at the level of myofilament proteins by a mechanism that may involve phosphorylation of troponin I by protein kinase C. (Circ Res.1995;77:114-120.)
ISSN:0009-7330
1524-4571