Changes in excitation-contraction coupling in an isolated ventricular myocyte model of cardiac stunning.
To investigate cardiac stunning, we recorded intracellular [Ca(2+)], contractions, and electrical activity in isolated guinea pig ventricular myocytes exposed to simulated ischemia and reperfusion. After equilibration, ischemia was simulated by exposing myocytes to hypoxia, acidosis, hyperkalemia, hypercapnia, lactate accumulation, and substrate deprivation for 30 min at 37 degrees C. Reperfusion was simulated by exposure to Tyrode solution. Field-stimulated myocytes exhibited stunning upon reperfusion. By 10 min of reperfusion, contraction amplitude decreased to 43.0 +/- 5.5% of preischemic values (n = 15, P < 0.05), although action potential configuration and sarcoplasmic reticulum Ca(2+) stores, assessed with caffeine, were normal. Diastolic [Ca(2+)] and Ca(2+) transients (fura 2) were also normal in stunned myocytes. In voltage-clamped cells, peak L-type Ca(2+) current was reduced to 47.4 +/- 4.5% of preischemic values at 10 min of reperfusion (n = 21, P < 0.05). Contractions elicited by Ca(2+)-induced Ca(2+) release and the voltage-sensitive release mechanism were both depressed in reperfusion. Our observations suggest that stunning is associated with reduced L-type Ca(2+) current but that alterations in Ca(2+) homeostasis and release are not directly responsible for stunning.
Cardiovascular Research Laboratories, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
William E
WE
Louch
Gregory R
GR
Ferrier
Susan E
SE
Howlett
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D017682:Myocardial Stunning; D009206:Myocardium / Q000473:pathology; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D016276:Ventricular Function
D002118:Calcium