Sodium current-induced calcium signals in isolated guinea-pig ventricular myocytes.
1. Na+ current (INa)-induced Ca2+ transients were studied in ventricular myocytes isolated from adult guinea-pig hearts. The fluorescent Ca2+ indicator fluo-3 or a mixture of fluo-3 and fura-red were used in conjunction with confocal microscopy to follow the intracellular Ca2+ concentration while membrane currents were measured simultaneously with the whole-cell configuration of the patch-clamp technique. 2. Ca2+ release from the sarcoplasmic reticulum (SR) could be triggered either by Ca2+ current (ICa) or Na+ current (INa). Analysis of INa-induced Ca2+ signals at higher temporal resolution revealed a faster upstroke of these transients when compared with those triggered by ICa. 3. In the presence of 20 microM ryanodine to block SR Ca2+ release ICa elicited a verapamil-sensitive Ca2+ transient with a slow upstroke. INa also induced a residual Ca2+ transient that was insensitive to 10 microM verapamil and characterized by a rapid upstroke. 4. The existence of a residual Ca2+ transient in the absence of SR Ca2+ release and L-type ICa indicates that INa is indeed able to evoke an increase in [Ca2+]i without uncontrolled activation of Ca2+ channels. 5. Substitution of extracellular Na+ by Li+ suppressed INa-induced Ca2+ transients, suggesting that the Ca2+ release and the residual Ca2+ transient can only be elicited by influx of Na+ and not by Li+. This result supports the notion that both the residual Ca2+ transient as well as the INa-induced Ca2+ release are mediated by the Na(+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipp
P
P
Department of Physiology, University of Bern, Switzerland.
Niggli
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007700:Kinetics; D008094:Lithium / Q000378:metabolism; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D015222:Sodium Channels; D012433:Ryanodine; D008094:Lithium; D014700:Verapamil; D002118:Calcium