Effects of phospholipase C on action potentials and intracellular Ca2+ concentration in guinea pig heart.
To clarify the role of phospholipase C (PLC) in arrythmias and cell injury during myocardial ischemia/reperfusion, we studied its effects on electrophysiology and [Ca2+]i in guinea pig hearts. After exposure to PLC (1 and 2 U/ml), the action potential durations of right ventricular papillary muscles were decreased. Delayed afterdepolarizations were observed in all of the preparations, and some developed into triggered activities. Developed tension decreased after an initial increase for the first 5 min, while resting tension increased consistently. The effects of PLC (0.02, 0.1, and 0.2 U/ml) on [Ca2+]i of ventricular myocytes were measured using fura-2 fluorescence. The ratio of rod-shaped cells to all cells decreased in a time- and a concentration-dependent manner. Perfusion with 0.1 U/ml PLC elevated [Ca2+]i from 56 +/- 5 nM to 245 +/- 47 nM before cell rounding, and to 1167 +/- 172 nM after cell rounding, suggesting that PLC causes Ca2+ overload. In conclusion, activation of PLC may play a role in arrhythmias and cell injury during ischemia/reperfusion. The increase in [Ca2+]i during ischemia/reperfusion may activate phospholipase, which would further increase [Ca2+]i to form a vicious cycle.
Third Department of Internal Medicine Hamamatsu University School of Medicine, Japan.
H
H
Hayashi
H
H
Miyata
H
H
Terada
N
N
Noda
H
H
Satoh
A
A
Kobayashi
N
N
Yamazaki
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010738:Type C Phospholipases / Q000502:physiology*
D010738:Type C Phospholipases; D002118:Calcium