SODIUM CURRENT-INDUCED CALCIUM SIGNALS IN ISOLATED GUINEA-PIG VENTRICULAR MYOCYTES

1. Na+ current (I-Na)-induced Ca2+ transients were studied in ventricu lar myocytes isolated from adult guinea-pig hearts. The fluorescent Ca 2+ indicator fluo-3 or a mixture of fluo-3 and fura-red were used in c onjunction with confocal microscopy to follow the intracellular Ca2+ c oncentration while membrane currents were measured simultaneously with the whole-cell configuration of the patch-clamp technique. 2. Ca2+ re lease from the sarcoplasmic reticulum (SR) could be triggered either b y Ca2+ current (I-Ca) or Na+ current (I-Na). Analysis of I-Na-induced Ca2+ signals at higher temporal resolution revealed a. faster upstroke of these transients when compared with those triggered by I-Ca. 3. In the presence of 20 mu M ryanodine to block SR Ca2+ release I-Ca elici ted a verapamil-sensitive Ca2+ transient with a slow upstroke. I-Na al so induced a residual Ca2+ transient that was insensitive to 10 mu M v erapamil and characterized by a rapid upstroke. 4. The existence of a residual Ca2+ transient in the absence of SR Ca2+ release and L-type I -Ca indicates that I-Na is indeed able to evoke an increase in [Ca2+]( i) without uncontrolled activation of Ca2+ channels. 5. Substitution o f extracellular Na+ by Li+ suppressed I-Na-induced Ca2+ transients, su ggesting that the Ca2+ release and the residual Ca2+ transient can onl y be elicited by influx of Naf and not by Li+. This result supports th e notion that both the residual Ca2+ transient as well as the I-Na-ind uced Ca2+ release are mediated by the Na+-Ca2+ exchange. 6. We conclud e that during I-Na [Na+] increased underneath the cell membrane and ac tivated the Ca2+ influx mode of the Na+-Ca2+ exchange. The Na+ current may serve as a safety factor in cardiac excitation-contraction coupli ng by accelerating the Ca2+ concentration changes responsible for sign al transduction in the subsarcolemmal space.