Lack of effect of isoproterenol on unloaded velocity of sarcomere shortening in rat cardiac trabeculae.
Several recent reports have indicated that catecholamines may act directly on the crossbridge cycle, independent of intracellular calcium concentration changes. The present study investigated the effect of isoproterenol on peak force during twitches at constant sarcomere length and unloaded velocity of sarcomere shortening in isolated right ventricular trabeculae of hearts with V1 or V3 isomyosin obtained from euthyroid and hypothyroid rats, respectively. Hypothyroidism was induced by treatment of the rats with propylthiouracil for 6 weeks. Electrophoretic analysis showed that the hearts of hypothyroid animals were composed only of V3 isomyosin, whereas the hearts of euthyroid animals were composed predominantly of V1 isomyosin. Force development was measured with a silicon strain gauge and sarcomere length with laser diffraction techniques; the shortening velocity was determined from contractions in which sarcomere length was initially held constant followed by a quick release to zero load and a controlled release at zero load. Both isometric twitch force and unloaded sarcomere shortening velocity were sigmoidal functions of [Ca2+]o and of the concentration of isoproterenol. At optimal [Ca2+]o, unloaded shortening velocity was 40% lower in myocardium of hypothyroid animals than in myocardium of euthyroid animals. Isoproterenol increased the sensitivity of isometric twitch force and unloaded shortening velocity to [Ca2+]o in trabeculae from both euthyroid and hypothyroid animals. Isoproterenol did not increase unloaded shortening velocity at optimal [Ca2+]o, regardless of the thyroid state. From these results we conclude that beta-adrenergic stimulation per se does not accelerate the rate limiting step in the crossbridge cycle that determines unloaded sarcomere shortening velocity in the intact cardiac cell.
de Tombe
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PP
Department of Medicine and Medical Physiology, University of Calgary, Alberta, Canada.
ter Keurs
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HE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000145:classification / Q000378:metabolism; D009994:Osmolar Concentration; D011441:Propylthiouracil; D051381:Rats; D011919:Rats, Inbred Strains; D012518:Sarcomeres / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D011441:Propylthiouracil; D009218:Myosins; D007545:Isoproterenol; D002118:Calcium