Rate-dependent abbreviation of Ca2+ transient in rat heart is independent of phospholamban phosphorylation.
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 hearts. Increasing stimulation rate from 0.1 to 0.5 and 1 Hz decreased the time taken for the Ca2+ transient to decline from its peak to 50% of its peak value in cells generating action potentials, when the duration of depolarization was held constant by voltage clamp, and when Na/Ca exchange was inhibited. The sarcoplasmic reticulum Ca2+ adenosinetriphosphatase inhibitor thapsigargin inhibited rate-dependent abbreviation of the Ca2+ transient. However, neither a chemical inhibitor of Ca(2+)-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 Ser16 and Thr17 of phospholamban showed no significant change in phosphorylation with changes of stimulation rate. These data suggest that rate-dependent shortening of the Ca2+ transient is due predominantly to enhanced Ca2+ uptake by the sarcoplasmic reticulum without changes in phospholamban phosphorylation.
Hussain
M
M
Department of Physiology, University of Leeds, United Kingdom.
Drago
G A
GA
Colyer
J
J
Orchard
C H
CH
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D005456:Fluorescent Dyes; D016257:Fura-2; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D016257:Fura-2; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban