HIGH-VOLTAGE-ACTIVATED CALCIUM CURRENT IN DEVELOPING NEURONS IS INSENSITIVE TO NIFEDIPINE

We have analyzed the effect of nifedipine on the macroscopic high-thre shold, voltage-activated (HVA) calcium current in four cell types: pos tnatal rat Purkinje and dorsal root ganglion (DRG) neurons, embryonic chick DRG neurons, and adult cat ventricular myocytes. As is consisten t with previous reports, nifedipine reduced HVA current in myocytes in a voltage-sensitive manner. Analysis of nifedipine actions on neurons , however, was compromised by slow inactivation of the current at hold ing potentials between -80 mV and -40 mV. The slow inactivation was vo ltage-dependent, Irreversible after 5 min, and contributed to ''rundow n'' of the current. At -40 mV, slow inactivation displayed two time co nstants: 12+/-8 s and 7+/-4 min. When slow inactivation was taken into account, we found no evidence for a nifedipine-sensitive component of the HVA current in these neurons. Consistent with previous studies, D RG neurons were reduced irreversibly by omega-conotoxin, whereas cardi ac and Purkinje cells were unaffected. Our biophysical and pharmacolog ical results consistent with two types of neuronal HVA currents (N typ e and P type) in developing neurons that are distinct from cardiac HVA currents (L type).