title: Altered cardiac sarcoplasmic reticulum function of intact myocytes of rat ventricle during metabolic inhibition.
abstract: Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca(2+) and the perforated patch-clamp technique to measure SR Ca(2+) content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca(2+) (sparks and waves of Ca(2+)-induced Ca(2+) release), increased SR Ca(2+) content (79.4+/-5.7 to 115.2+/-6.6 micromol/L cell volume [mean+/-SEM; P:<0.001]), and, after a wave of Ca(2+) release, slower reuptake of Ca(2+) into the SR (rate constant of fall of Ca(2+) reduced from 8.5+/-1.1 s(-)(1) in control to 5.2+/-0.4 s(-)(1) in metabolic inhibition [P:<0.01]). Inhibition of L-type Ca(2+) channels with Cd(2+) (100 micromol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca(2+) sparks. These results are evidence of inhibition of both Ca(2+) release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca(2+) content at the time of reduced frequency of spontaneous release of Ca(2+) shows that the dominant effect of metabolic inhibition is to inhibit release of Ca(2+) from the SR, allowing the accumulation of greater than normal amounts of Ca(2+). In the context of ischemia, this extra accumulation of Ca(2+) would present a risk of potentially arrhythmogenic, spontaneous release of Ca(2+) on reperfusion of the tissue.
authors.affiliation: Department of Medicine, University of Manchester, Manchester, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Overend
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
authors.forename: S C
authors.initials: SC
authors.lastname: O'Neill
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005456:Fluorescent Dyes; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D018613:Microscopy, Confocal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003486:Cyanides; D005456:Fluorescent Dyes; D019837:Ryanodine Receptor Calcium Release Channel; D014966:Xanthenes; D002104:Cadmium; C059715:Fluo-3; D003847:Deoxyglucose; D000252:Calcium-Transporting ATPases; D002118:Calcium