Methyl mercury reduces voltage-activated currents of rat dorsal root ganglion neurons.
Methyl mercury (MeHg) is a widespread toxicant with major actions on the nervous system. Since the function of neurons depends on voltage gated ion channels, we examined the effects of micromolar concentrations of methyl mercury on voltage-activated calcium, potassium and sodium channel currents of cultured rat dorsal root ganglion (DRG) neurons. The cells, which were obtained from 2-4 day old rat pups, were whole-cell patch-clamped. Currents were separated by selective intra- and extracellular solutions as well as specific depolarizing voltage steps. We did not distinguish between different calcium, potassium or sodium channel subtypes. All three types of voltage-activated currents were irreversibly reduced by MeHg in a concentration dependent manner. Voltage-activated calcium and potassium channel currents were more sensitive to MeHg (Calcium: IC50 = 2.6 +/- 0.4 microM; Potassium: IC50 = 2.2 +/- 0.3 microM) than voltage-activated sodium channels (IC50 = 12.3 +/- 2.0 microM). The Hill coefficients for the reduction of the currents were calculated as approximately 1 for calcium and potassium channel currents and as 1.7 for sodium currents. In the cases of the voltage-activated calcium and sodium channel currents the reduction was clearly use dependent. Higher concentrations of MeHg (> or = 5 microM) resulted in a biphasic change in the holding membrane current at the potential of -80 mV in approximately 25% of the cases.
Institut für Neuroinformatik, Bochum, Germany.
R
R
Leonhardt
H
H
Haas
D
D
Büsselberg
D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000494:pharmacology* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D007473:Ion Channels; D008767:Methylmercury Compounds; D015221:Potassium Channels; D015222:Sodium Channels