Blockade of mammalian and invertebrate calcium channels by lead

Dietrich Busselberg, M. L. Evans, H. L. Haas, D. O. Carpenter

Research output: Contribution to journalArticle

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Abstract

We have compared the effects of Pb2+ on voltage-dependent calcium channels of the marine mollusc Aplysia, studied with a two electrode voltage clamp, with those on calcium channels in cultured rat dorsal root ganglion (DRG) neurons studied with whole cell patch clamp. In both preparations Pb2+ was a potent blocker of calcium channel currents at concentrations that did not significantly affect potassium and sodium currents. The blockade was concentration dependent and the percentage of blockade was reduced when the concentration of the charge carrier was elevated. In Aplysia the threshold Pb2+ concentration was about 1 μM, and the Hill coefficient near 1.0 under all conditions. Pb2+ did not significantly change inactivation but shifted the voltage dependence of activation to hyperpolarized voltages in a dose-dependent manner. The blockade of calcium currents by Pb2+ was highly voltage dependent and increased with depolarization. Rat dorsal root ganglion cells exhibit three different types of voltage-dependent calcium channels (N, L and T) which can be distinguished by the potential at which the channel activates or inactivates and by their sensitivity to pharmacologic antagonists. The IC50 for blockade of the L current was 1.03 μM with a Hill slope of 1.15. Currents elicited by voltage steps which activate N plus L currents had an IC50 of 0.64 μM and a Hill slope of 1.16. T currents were less sensitive, having an IC50 of 6 μM. Sodium and potassium currents were relatively unaffected in both preparations at concentrations at which the calcium channel was blocked more than 60% (1 μM or 200 μM respectively). The blockade in DRG neurons was less voltage- dependent and reversible than that in the invertebrate model system. These observations indicate that Pb2+ is a potent, reversible and selective blocker of voltage-dependent calcium channels at low concentrations.

Original languageEnglish
Pages (from-to)249-258
Number of pages10
JournalNeuroToxicology
Volume14
Issue number2-3
Publication statusPublished - 1993
Externally publishedYes

Fingerprint

Invertebrates
Calcium Channels
Spinal Ganglia
Inhibitory Concentration 50
Aplysia
Electric potential
Potassium
Sodium
T-Type Calcium Channels
N-Type Calcium Channels
Clamping devices
Neurons
L-Type Calcium Channels
Rats
Mollusca
Calcium Channel Blockers
Molluscs
Electrodes
Depolarization
Calcium

Keywords

  • Aplysia Neurons
  • Lead (Pb)
  • Rat Dorsal Root Ganglion (DRG) Cells
  • Voltage-Gated Calcium Channels

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Toxicology

Cite this

Busselberg, D., Evans, M. L., Haas, H. L., & Carpenter, D. O. (1993). Blockade of mammalian and invertebrate calcium channels by lead. NeuroToxicology, 14(2-3), 249-258.

Blockade of mammalian and invertebrate calcium channels by lead. / Busselberg, Dietrich; Evans, M. L.; Haas, H. L.; Carpenter, D. O.

In: NeuroToxicology, Vol. 14, No. 2-3, 1993, p. 249-258.

Research output: Contribution to journalArticle

Busselberg, D, Evans, ML, Haas, HL & Carpenter, DO 1993, 'Blockade of mammalian and invertebrate calcium channels by lead', NeuroToxicology, vol. 14, no. 2-3, pp. 249-258.
Busselberg D, Evans ML, Haas HL, Carpenter DO. Blockade of mammalian and invertebrate calcium channels by lead. NeuroToxicology. 1993;14(2-3):249-258.
Busselberg, Dietrich ; Evans, M. L. ; Haas, H. L. ; Carpenter, D. O. / Blockade of mammalian and invertebrate calcium channels by lead. In: NeuroToxicology. 1993 ; Vol. 14, No. 2-3. pp. 249-258.
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