title: Beta-myosin heavy chain myocytes are more resistant to changes in power output induced by ischemic conditions.
abstract: During ischemia intracellular concentrations of P(i) and H+ increase. Also, changes in myosin heavy chain (MHC) isoform toward beta-MHC have been reported after ischemia and infarction associated with coronary artery disease. The purpose of this study was to investigate the effects of myoplasmic changes of P(i) and H+ on the loaded shortening velocity and power output of cardiac myocytes expressing either alpha- or beta-MHC. Skinned cardiac myocyte preparations were obtained from adult male Sprague-Dawley rats (control or treated with 5-n-propyl-2-thiouracil to induce beta-MHC) and mounted between a force transducer and servomotor system. Myocyte preparations were subjected to a series of isotonic force clamps to determine shortening velocity and power output during Ca2+ activations in each of the following solutions: 1) pCa 4.5 and pH 7.0; 2) pCa 4.5, pH 7.0, and 5 mM P(i); 3) pCa 4.5 and pH 6.6; and 4) pCa 4.5, pH 6.6, and 5 mM P(i). Added P(i) and lowered pH each caused isometric force to decline to the same extent in alpha-MHC and beta-MHC myocytes; however, beta-MHC myocytes were more resistant to changes in absolute power output. For example, peak absolute power output fell 53% in alpha-MHC myocytes, whereas power fell only 38% in beta-MHC myocytes in response to elevated P(i) and lowered pH (i.e., solution 4). The reduced effect on power output was the result of a greater increase in loaded shortening velocity induced by P(i) in beta-MHC myocytes and an increase in loaded shortening velocity at pH 6.6 that occurred only in beta-MHC myocytes. We conclude that the functional response to elevated P(i) and lowered pH during ischemia is MHC isoform-dependent with beta-MHC myocytes being more resistant to declines in power output.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Hinken
authors.forename: Kerry S
authors.initials: KS
authors.lastname: McDonald
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D009119:Muscle Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D024723:Ventricular Myosins / Q000037:antagonists & inhibitors
chemical_list: D000963:Antimetabolites; C000594638:MYH7 protein, rat; D010710:Phosphates; D011441:Propylthiouracil; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains