Methyl mercury reduces voltage-activated currents of rat dorsal root ganglion neurons

Ralph Leonhardt, Helmut Haas, Dietrich Busselberg

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 μM; Potassium: IC50 = 2.2 ± 0.3 μM) than voltage-activated sodium channels (IC50 = 12.3 ± 2.0 μM). The Hill coefficients for the reduction of the currents were calculated as ~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 (≤5 μM) resulted in a biphasic change in the holding membrane current at the potential of -80 mV in ~25% of the cases.

Original languageEnglish
Pages (from-to)532-538
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume354
Issue number4
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Sodium Channels
Spinal Ganglia
Calcium Channels
Mercury
Potassium Channels
Inhibitory Concentration 50
Neurons
Calcium-Activated Potassium Channels
Ion Channels
Nervous System
Potassium
Sodium
Calcium
Membranes

Keywords

  • Calcium channels
  • Methyl mercury (CHHgCl)
  • Neurotoxicity
  • Potassium channels
  • Rat DRG neurons
  • Sodium channels
  • Whole-cell patch-clamp

ASJC Scopus subject areas

  • Pharmacology

Cite this

Methyl mercury reduces voltage-activated currents of rat dorsal root ganglion neurons. / Leonhardt, Ralph; Haas, Helmut; Busselberg, Dietrich.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 354, No. 4, 1996, p. 532-538.

Research output: Contribution to journalArticle

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AU - Haas, Helmut

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N2 - 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 μM; Potassium: IC50 = 2.2 ± 0.3 μM) than voltage-activated sodium channels (IC50 = 12.3 ± 2.0 μM). The Hill coefficients for the reduction of the currents were calculated as ~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 (≤5 μM) resulted in a biphasic change in the holding membrane current at the potential of -80 mV in ~25% of the cases.

AB - 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 μM; Potassium: IC50 = 2.2 ± 0.3 μM) than voltage-activated sodium channels (IC50 = 12.3 ± 2.0 μM). The Hill coefficients for the reduction of the currents were calculated as ~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 (≤5 μM) resulted in a biphasic change in the holding membrane current at the potential of -80 mV in ~25% of the cases.

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