Mercury (Hg2+) decreases voltage-gated calcium channel currents in rat DRG and Aplysia neurons.
Inorganic mercury (Hg2+) reduced voltage-gated calcium channel currents irreversibly in two different preparations. In cultured rat dorsal root ganglion (DRG) neurons, studied with the whole cell patch clamp technique, a rapid concentration-dependent decrease in the L/N-type currents to a steady state was observed with an IC50 of 1.1 microM and a Hill coefficient of 1.3. T-currents were blocked with Hg2+ in the same concentration range (0.5-2 microM). With increasing Hg2+ concentrations a slow membrane current was additionally activated, most obviously at concentrations over 2 microM Hg2+. This current was irreversible and might be due to the opening of other (non-specific) ion channels by Hg2+. The current-voltage (I-V) relation of DRG neurons shifted to more positive values, suggesting a binding of Hg2+ to the channel protein and/or modifying its gating properties. In neurons of the abdominal ganglion of Aplysia californica, studied with the two electrode voltage clamp technique, a continuous decrease of calcium channel currents was seen even with the lowest used concentration of Hg2+ (5 microM). A steady state was not reached and the effect was irreversible without any change on resting membrane currents, even with high concentrations (up to 50 microM). No shift of the I-V relation of the calcium channel currents was observed. Effects on voltage-activated calcium channel currents with Hg2+ concentrations such low have not been reported before. We conclude that neurotoxic effects of inorganic mercury could be partially due to the irreversible blockade of voltage-activated calcium channels.
Pekel
M
M
Physiologisches Institut II Heinrich-Heine Universität Düsseldorf, Germany.
Platt
B
B
Büsselberg
D
D
D000818:Animals; D000831:Animals, Newborn; D001048:Aplysia; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017952:Ganglia, Invertebrate / Q000502:physiology; D005727:Ganglia, Spinal / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008628:Mercury / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D015220:Calcium Channels; D008628:Mercury