Unitary current analysis of L-type Ca2+ channels in human fetal ventricular myocytes

Calcium Channels in Human Fetal Heart. Introduction: L-type calcium channel s were studied in cell-attached patches from ventricular cell membranes of human fetal heart. Methods and Results: Experiments were performed in the presence of 70 mM Ba 2+ as the charge carrier at 22 degrees C to 24 degrees C. Unitary current s weeps were evoked by 300-msec depolarizing pulses to 0 mV from a holding po tential of -50 mV at 0.5 Hz. Recorded currents were blocked by nisoldipine (1 mu M) and stimulated by (-)Bay K 8644 (1 mu M). During control, channel activity was seen in 13.9% +/- 4.2% of the total 200 sweeps. Ensemble avera ge current amplitude was 0.03 +/- 0.01 pA (n = 6) and average conductance w as 20.4 +/- 0.2 pS (n = 5). Analysis of single channel kinetics showed open time and closed time histograms were best fit by one and two exponentials, respectively. Mean open time was tau(o) = 0.99 +/- 0.05 msec (n = 6). Mean closed time fast (tau(cf)) and slow (tau(cs)) component values were tau(c f) = 0.85 +/- 0.09 msec and tau(cs) = 8.0 +/- 0.94 msec (n = 6), respective ly. With intrapipette (-)Bay K 8644 (1 mu M), mean open time was best fit b y two exponentials, tau(cf) = 0.9 +/- 0.2 msec (n = 10) and tau(os) = 13.4 +/- 2.6 msec (n = 10); mean close time values were tau(cf) = 0.6 +/- 0.1 ms ec (n =10) and tau(cs) = 9.8 +/- 1.9 msec (n =10), respectively. With (-)Ba y K 8644, channel activity was 66.5% +/- 7.4%, the ensemble average current was 0.52 +/- 0.04 pA (n = 10) and the conductance 20.7 +/- 0.5 pS (n = 5). Conclusion: (1) the data establishes the characteristics of L-type Ca chann els of human fetal hearts and their modulation by dihydropyridines; (2) the open time kinetics differ from those of avian embryonic and rat fetal hear ts; and (3) the findings provide new and relevant information for understan ding the physiologic behavior of unitary Ca2+ channels in the developing hu man heart and the baseline comparison for diseases that implicate Ca2+ chan nels in their etiology, such as autoimmune-associated congenital heart bloc k. (J Cardiovasc Electrophysiol, Vol. 10, pp. 682-700, May 1999).