Role of adenosine triphosphate and protein kinase a in the force-frequency relationship in isolated rat cardiomyocytes

Abstract

The physiological heart rate of rodents is around 4-6 Hz, although a stimulus frequency of 1 Hz is generally used in isolated cardiomyocytes to study changes in the contraction-relaxation cycle in cardiac muscle physiology and pathophysiology. Our study investigated the contraction parameters in isolated cardiomyocytes at 1, 2 and 4 Hz stimulation, and the roles of ATP and protein kinase A (PKA) in the force-frequency relationship in isolated cardiomyocytes. The contraction of the cell and intracellular Ca2+ changes were recorded simultaneously during cell stimulation by applying pulses of 6-8 V amplitude with frequencies of 1, 2 and 4 Hz. The increase in stimulus frequency caused a significant decrease in the percentage of shortening, relaxation times, slowing of the relaxation rate, and a significant increase in diastolic Ca2+ levels, but had no effect on the contraction rate and Ca2+ transients. Administration of ATP and N6-benzoyladenosine-3?-5?-cyclic monophosphate (6-BNZcAMP) caused an increase in contraction amplitude and speed which were proportional to the stimulus frequency but had no effect on the relaxation times. The experimental results show that the forcestimulus frequency has a negative correlation in isolated myocytes and that energy metabolism and the ?-adrenergic system may be responsible for this relationship.