Creatine kinase (CK) plays a crucial role in myocardial energy metabolism.
Alterations in CK gene expression are found in hypertrophied and
failing heart, 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 distribution and -gene expression that are
characteristic of the failing and hypertrophied heart. Isolated rat
hearts were perfused (constant pressure of 80 mmHg) with red cell
suspensions. Following a 20-min warm-up period, perfusion 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
distribution 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. There were no significant differences
among the three groups in total CK-activity and in distribution of
CK-MM, CK-BB, CK-MB and mito-CK. Thus, beta-adrenergic 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.