β-myosin heavy chain myocytes are more resistant to changes in power output induced by ischemic conditions

beta-Myosin heavy chain myocytes are more resistant to changes in power output induced by ischemic conditions. Am J Physiol Heart Circ Physiol 290: H869-H877, 2006. First published September 19, 2005; doi:10.1152/ajpheart.00221.2005.-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 Pi. Added Pi and lowered pH each caused isometric force to decline to the same extent in beta-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 Pi 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 Pi 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 Pi and lowered pH during ischemia is MHC isoform-dependent with beta-MHC myocytes being more resistant to declines in power output.