THE EFFECTS OF INORGANIC LEAD ON VOLTAGE-SENSITIVE CALCIUM CHANNELS DIFFER AMONG CELL-TYPES AND AMONG CHANNEL SUBTYPES

The whole-cell version of patch clamping was used to compare the effec ts of acute in vitro exposure to inorganic lead (Pb2+) on voltage-sens itive calcium channels in cultured N 1 E- 1 15 mouse neuroblastoma cel ls and E18 rat hippocampal neurons. Free Pb2+ concentrations in saline s with a high lead-buffering capacity were measured with a calibrated Pb2+-selective electrode. Previously, we found that N1E-115 neurons co ntain low voltage activated, rapidly inactivating (T) channels and hig h voltage activated, slowly inactivating (L) channels. Pb2+ inhibits b oth channel subtypes in N1E-115 cells, with some selectivity against L -type channels (IC50 approximately 700 nM free Pb2+ for L-type channel s, 1300 nM free Pb2+ for T-type channels; Audesirk and Audesirk, 1991) . In addition to T-type and L-type channels, cultured E18 rat hippocam pal neurons have been reported to contain high voltage-activated, rapi dly inactivating (N) channels. In our experiments with 5 to 20 day old cultures, almost all neurons showed substantial L-type current, appro ximately half showed significant N-type current, and fewer than 5% sho wed significant T-type current. We found that Pb2+ is somewhat selecti ve against L-type channels (IC50 approximately 30 nM free Pb2+ in 10 m M Ba2+ as the charge carrier, 55 nM in 50 mM Ba2+) compared to N-chann els (IC50 approximately 80 nM free Pb2+ in 10 mM Ba2+, 200 nM in 50 mM Ba2+). These results suggest that the effects of Pb2+ on calcium chan nels of vertebrate neurons vary both among cell types and among channe l subtypes. (C) 1993 Intox Press, Inc.