RATE-DEPENDENT ABBREVIATION OF CA2-HEART IS INDEPENDENT OF PHOSPHOLAMBAN PHOSPHORYLATION( TRANSIENT IN RAT)

The mechanisms underlying the accelerated decline of the intracellular Ca2+ transient that occurs in cardiac muscle when stimulation rate is increased have been investigated in ventricular myocytes from rat hea rts. Increasing stimulation rate from 0.1 to 0.5 and 1 Hz decreased th e time taken for the Ca2+ transient to decline from its peak to 50% of its peak value in cells generating action potentials, when the durati on of depolarization was held constant by voltage clamp, and when Na/C a exchange was inhibited. The sarcoplasmic reticulum Ca2+ adenosinetri phosphatase inhibitor thapsigargin inhibited rate-dependent abbreviati on of the Ca2+ transient. However, neither a chemical inhibitor of Ca2 +-calmodulin-dependent protein kinase II(KN62) nor a peptide inhibitor of this enzyme (calmodulin-binding domain peptide) had a significant effect on rate-dependent abbreviation of the Ca2+ transient. Analysis of the phosphorylation of the regulatory sites Ser(16) and Thr(17) of phospholamban showed no significant change in phosphorylation with cha nges of stimulation rate. These data suggest that rate-dependent short ening of the Ca2+ transient is due predominantly to enhanced Ca2+ upta ke by the sarcoplasmic reticulum without changes in phospholamban phos phorylation.