Phase I and phase II of short-term mechanical restitution in perfused rat left ventricles.
We examined the contributions of the Ca(2+) channels of the sarcolemma and of the sarcoplasmic reticulum to electromechanical restitution. Extrasystoles (F(1)) were interpolated 40-600 ms following a steady-state beat (F(0)) in perfused rat ventricles paced at 2 or 3 Hz. Plots of F(1)/F(0) versus the extrasystolic interval consisted of phase I, which occurred before relaxation of the steady-state beat, and phase II, which occurred later. Phase I exhibited a period of enhanced left ventricular pressure development that coincided with action potential prolongation. Phase I was eliminated by -BAY K 8644 (100 nM) and FPL 64176 (150 nM), augmented by 3 microM thapsigargin plus 200 nM ryanodine and unaffected by KN-93 and KB-R7943. Phase II was accelerated by the Ca(2+) channel agonists and by isoproterenol but was eliminated by thapsigargin plus ryanodine. The results suggest that phase I of electromechanical restitution is caused by a transient L-type Ca(2+) current facilitation, whereas phase II represents the recovery of the ability of the sarcoplasmic reticulum to release Ca(2+).
Dumitrescu
Cristian
C
The Ohio State University Biophysics Program and Dorothy M. Davis Heart and Lung Research Institute, Columbus 43210, USA.
Narayan
Prakash
P
Cheng
Yuanna
Y
Efimov
Igor R
IR
Altschuld
Ruth A
RA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012508:Sarcolemma / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013599:Systole; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation; D016277:Ventricular Function, Left / Q000502:physiology*; D000096926:Benzenesulfonamides
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001596:Benzylamines; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007545:Isoproterenol; D011758:Pyrroles; D012433:Ryanodine; D013449:Sulfonamides; D019284:Thapsigargin; C071658:FPL 64176; C072105:KN 93; D000096926:Benzenesulfonamides