Strang K T, Moss R L
Department of Physiology, School of Medicine, University of Wisconsin, Madison, USA.
Circ Res. 1995 Jul;77(1):114-20. doi: 10.1161/01.res.77.1.114.
alpha 1-Adrenergic agonists have negative inotropic effects on mammalian myocardium under some conditions, and biochemical experiments measuring the Ca(2+)-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 alpha 1-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 alpha 1-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 [Ca2+] was also assessed for each myocyte. Vo was significantly lower in the alpha 1-adrenergic receptor agonist-treated cells than in the control cells, but there was no effect on Ca2+ 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 alpha 1-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.
