Key points are not available for this paper at this time.
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 et al. (Tue,) studied this question.