Acute changes of myocardial creatine kinase gene expression under beta-adrenergic stimulation

Creatine kinase (CK) plays a crucial role in myocardial energy metabolism. Alterations in CK gene expression are found in hypertrophied and failing he art, but the mechanisms behind these changes are unclear. This study tests the hypothesis that increased adrenergic stimulation, which is observed in heart failure, induces changes of myocardial CK-activity, -isoenzyme distri bution and -gene expression that are characteristic of the failing and hype rtrophied heart. Isolated rat hearts were perfused (constant pressure of 80 mmHg) with red cell suspensions. Following a 20-min warm-up period, perfus ion for 3 h with 10(-8) M (iso 3 h) or without (control 3 h) isoproterenol was started or experiments were immediately terminated (control 0 h). Left ventricular tissue was analyzed for total CK-activity, CK-isoenzyme distrib ution and, by use of quantitative RT-PCR, for B-CK, M-CK, mito-CK and GAPDH - (as internal standard) mRNA. After beta -adrenergic stimulation (iso 3 h) but not after control perfusion (control 3 h) a roughly threefold increase in B-CK mRNA levels and a decrease in M-CK mRNA levels by 18% was found. T here were no significant differences among the three groups in total CK-act ivity and in distribution of CK-MM, CK-BB, CK-MB and mito-CK. Thus, beta -a drenergic stimulation induces a switch in CK gene expression from M-CK to B -CK, which is characteristic for the hypertrophied and failing heart. This may be interpreted as an adaptive mechanism making energy transduction via CK more efficient at times of increased metabolic demand. (C) 2000 Elsevier Science B.V. All rights reserved.