Novel type of ion channel activated by Pb2+, Cd2+, and Al3+ in cultured mouse neuroblastoma cells.
Superfusion with Pb2+ induces a slow, noninactivating and reversible inward current in voltage-clamped N1E-115 neuroblastoma cells. The amplitude of this inward current increases in the range of 1-200 microM Pb/+. Single-channel patch-clamp experiments have revealed that this inward current is mediated by discrete ion channels. Reversal potentials from linear I-V relationships are close to 0 mV for whole-cell and single-channel currents and the single-channel conductance amounts to 24 pS. The Pb2(+)-induced membrane current is not mediated by various known types of ion channels, since it is not blocked by external tetrodotoxin, tetraethylammonium, D-tubocurarine, atropine, ICS 205-930 and by internal EGTA. In Na(+)-free solutions superfusion with Pb2+ neither evokes a whole-cell inward current, nor single-channel openings. At -80 mV the open-time distribution of the single channels activated by 1 microM Pb2+ is dual exponential with time constants of 17 and 194 msec. When the Pb2+ concentration is increased from 1 to 20 microM these time constants decrease to 2 and 13 msec, but the amplitude of single-channel currents remains -1.9 nA. Cd2+ and Al3+ induce inward currents and single-channel openings similar to Pb2+. Time constants fitted to the open-time distribution of single channels are 14 and 135 msec in the presence of 1 microM Cd2+ and 15 and 99 msec in the presence of 50 microM Al3+. Conversely, Cu2+ induces an irreversible inward current in neuroblastoma cells. Single-channel openings are undetected in the presence of Cu2+ and in Na(+)-free solutions Cu2+ is still able to induce an inward current. It is concluded that Pb2+, Cd2+ and possibly Al3+ activate a novel type of metal ion-activated (MIA) channel in N1E-115 cells.
Research Institute of Toxicology, University of Utrecht, The Netherlands.
M
M
Oortgiesen
R G
RG
van Kleef
H P
HP
Vijverberg
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D007854:Lead / Q000494:pharmacology*; D008564:Membrane Potentials; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D007473:Ion Channels; D002104:Cadmium; D007854:Lead; D003300:Copper; D000535:Aluminum