Abstract
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+).
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
-
Action Potentials / physiology
-
Animals
-
Benzylamines / pharmacology
-
Calcium Channel Agonists / pharmacology
-
Calcium Channel Blockers / pharmacology
-
Calcium Channels / drug effects
-
Calcium Channels / physiology*
-
Enzyme Inhibitors / pharmacology
-
Heart / drug effects
-
Heart / physiology*
-
Heart Rate
-
In Vitro Techniques
-
Isoproterenol / pharmacology
-
Male
-
Perfusion
-
Pyrroles / pharmacology
-
Rats
-
Rats, Sprague-Dawley
-
Ryanodine / pharmacology
-
Sarcolemma / physiology
-
Sarcoplasmic Reticulum / physiology*
-
Sulfonamides / pharmacology
-
Systole
-
Thapsigargin / pharmacology
-
Time Factors
-
Vasodilation
-
Ventricular Function, Left / physiology*
Substances
-
Benzylamines
-
Calcium Channel Agonists
-
Calcium Channel Blockers
-
Calcium Channels
-
Enzyme Inhibitors
-
Pyrroles
-
Sulfonamides
-
FPL 64176
-
KN 93
-
Ryanodine
-
Thapsigargin
-
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
-
Isoproterenol