Abstract
The effects of inorganic lead (Pb 2+) on the ion currents mediated by (1) neuronal nicotinic acetylcholine (ACh) receptors, (2) serotonin 5-HT 3 receptors, as well as (3) voltage-dependent Ca 2+ and Na + channels have been investigated in voltage clamped mouse neuroblastoma cells. The nicotinic ACh receptor-ion channel complex appeared more sensitive to Pb 2+ than the other ion channels investigated. Low concentrations of Pb 2+ (1 n m – 3 μ m) reduced the peak amplitude of the ACh-induced inward current to 74%–10% of the control value in a concentration-dependent manner. However, between 10 μ m and 100 μ m Pb 2+ the blocking effect was reversed, while the decay of the ACh-induced inward current was delayed. These effects of Pb 2+ on the nicotinic receptor-mediated inward current can be described by the sum of two sigmoidal concentration-effect curves with an IC50 value of 19 n m and an EC50 of 21 μ m and with slope factors of −0.5 and 0.8, respectively. The current mediated by 5-HT 3 receptors was less potently blocked by Pb 2+ (IC50 = 49 μ m; slope factor = −0.3). In addition, Pb 2+ blocked the ion current through voltage-dependent Ca 2+ channels. The IC50 value of the concentration-effect curve of block of transient type Ca 2+ channels by Pb 2+ is 4.8 μ m and the slope factor is −0.9. Voltage-dependent Na + channels were not affected by Pb 2+ up to 100 μ m. At concentrations > 1 μ m, Pb 2+ also induced a noninactivating inward current. The present results show that modification of neuronal nicotinic receptor function may contribute to neurotoxic effects of Pb 2+ poisoning.
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