Coordinated control of cell Ca(2+) loading and triggered release from the sarcoplasmic reticulum underlies the rapid inotropic response to increased L-type Ca(2+) current.
The aim of this study was to investigate how sarcoplasmic reticulum (SR) Ca(2+) content and systolic Ca(2+) are controlled when Ca(2+) entry into the cell is varied. Experiments were performed on voltage-clamped rat and ferret ventricular myocytes loaded with fluo-3 to measure intracellular Ca(2+) concentration ([Ca(2+)](i)). Increasing external Ca(2+) concentration ([Ca(2+)](o)) from 1 to 2 mmol/L increased the amplitude of the systolic Ca(2+) transient with no effect on SR Ca(2+) content. This constancy of SR content is shown to result because the larger Ca(2+) transient activates a larger Ca(2+) efflux from the cell that balances the increased influx. Decreasing [Ca(2+)](o) to 0.2 mmol/L decreased systolic Ca(2+) but produced a small increase of SR Ca(2+) content. This increase of SR Ca(2+) content is due to a decreased release of Ca(2+) from the SR resulting in decreased loss of Ca(2+) from the cell. An increase of [Ca(2+)](o) has two effects: (1) increasing the fraction of SR Ca(2+) content, which is released on depolarization and (2) increasing Ca(2+) entry into the cell. The results of this study show that the combination of these effects results in rapid changes in the amplitude of the systolic Ca(2+) transient. In support of this, the changes of amplitude of the transient occur more quickly following changes of [Ca(2+)](o) than following refilling of the SR after depletion with caffeine. We conclude that the coordinated control of increased Ca(2+) entry and greater fractional release of Ca(2+) is an important factor in regulating excitation-contraction coupling.
Trafford
A W
AW
Unit of Cardiac Physiology, University of Manchester, Manchester, UK.trafford@man.ac.uk
Díaz
M E
ME
Eisner
D A
DA
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000814:Aniline Compounds; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D005289:Ferrets; D005456:Fluorescent Dyes; D007424:Intracellular Fluid / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013599:Systole / Q000502:physiology; D014966:Xanthenes
D000814:Aniline Compounds; D020746:Calcium Channels, L-Type; D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; D019831:Sodium-Calcium Exchanger; D014966:Xanthenes; C059715:Fluo-3; D001464:Barium; D002110:Caffeine; D015761:4-Aminopyridine; D002118:Calcium