Lead reduces depolarization-induced calcium entry in cultured DRG neurons without crossing the cell membrane: fura-2 measurements.
1. Cultured dorsal root ganglion of rat pups were depolarized by exposure to 50 mM K+ and the rise of [Ca2+]i was measured using fura-2 as an indicator. 2. Lead in the extracellular solution reduced the rise of [Ca2+]i in a concentration-dependent manner, with a threshold concentration of 0.25 microM. More than 80% of the calcium entry was prevented by approximately 5 microM lead. The IC50 and the Hill coefficient were 3.1 microM and 1, respectively. 3. This effect was considered to be due to a reduction of VACCCs, since applications of NMDA did not result in any rise of [Ca2+]i. 4. Since Pb2+ itself changes the fura-2 signal in a typical and characteristic manner, fura-2 is also an indicator for Pb2+. No changes in fura-2 signals were detected when lead (5 microM) was applied for several minutes in the absence of calcium, indicating that Pb2+ did not enter the cells. 5. Thus it is concluded that lead prevents calcium entry by reducing VACCCs but does not cross the cell membrane itself.
Domann
R
R
Physiologisches Institut II, Heinrich-Heine Universität, Düsseldorf, Germany.
Wunder
L
L
Büsselberg
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects; D007854:Lead / Q000378:metabolism / Q000633:toxicity*; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions / Q000737:chemistry
D015220:Calcium Channels; D005456:Fluorescent Dyes; D007473:Ion Channels; D012996:Solutions; D007854:Lead; D016202:N-Methylaspartate; D008274:Magnesium; D011188:Potassium; D002118:Calcium; D016257:Fura-2