Mammalian voltage-activated calcium channel currents are blocked by Pb2+, Zn2+, and Al3+

Dietrich Busselberg, B. Platt, D. Michael, D. O. Carpenter, H. L. Haas

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Abstract

1. The effects of the di- and trivalent trace metal cations, Pb2+, Zn2+, and Al3+, on voltage-activated calcium channel currents recorded from cultured rat dorsal root ganglion neurons were determined. 2. All three cations blocked transient and sustained components of the voltage-gated calcium channel currents elicited by a voltage jump from -80 mV to 0 mV, but the trace metals differed in threshold, reversibility, and specificity, and in actions on the different components. 3. Pb2+ was most effective in reducing the voltage-activated calcium channel currents. Threshold concentration for Pb2+ was <0.1 μM. The threshold for Zn2+ action was <5 μM and that for Al3+ was ~20 μM. Total blockade (>80%) was obtained with concentrations >1 μM Pb2+, and 150-200 μM Zn2+ or Al3+. Half of the current was blocked with 0.6 μM Pb2+, 69 μM Zn2+, and 84 μM Al3+. The Hill slope for Pb2+ and Zn2+ action was ~1, whereas for Al3+ it was close to 3. 4. Al3+ blockade was clearly use dependent, whereas this was not the case for either Pb2+ or Zn2+. 5. The blockade by none of these metals was totally reversible. The best recovery was obtained upon wash after exposure to Pb2+ (≥60%), some recovery was seen with Zn2+ (≥50%), but there was little or no recovery after application of Al3+. 6. With Zn2+ or Al3+ in the external solution the current-voltage relation often shifted to depolarized voltages. The degree of the shift was a function of concentration, but differed from cell to cell and was probably because of a charge-screening action. 7. The actions of Pb2+ and Al3+ are relatively specific for voltage-activated calcium channels. Concentrations that block the voltage-activated calcium channel currents by >80% (1 μM Pb2+ or 200 μM Al3+) had little effect (<20%) on voltage-activated potassium or sodium channel currents. The effects of Zn2+ were less specific.

Original languageEnglish
Pages (from-to)1491-1497
Number of pages7
JournalJournal of Neurophysiology
Volume71
Issue number4
Publication statusPublished - 1994
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Busselberg, D., Platt, B., Michael, D., Carpenter, D. O., & Haas, H. L. (1994). Mammalian voltage-activated calcium channel currents are blocked by Pb2+, Zn2+, and Al3+ . Journal of Neurophysiology, 71(4), 1491-1497.