Mammalian voltage-activated calcium channel currents are blocked by Pb2+, Zn2+, and Al3+.
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 microM. The threshold for Zn2+ action was < 5 microM and that for Al3+ was approximately 20 microM. Total blockade (> 80%) was obtained with concentrations > 1 microM Pb2+, and 150-200 microM Zn2+ or Al3+. Half of the current was blocked with 0.6 microM Pb2+, 69 microM Zn2+, and 84 microM Al3+. The Hill slope for Pb2+ and Zn2+ action was approximately 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+ (> or = 60%), some recovery was seen with Zn2+ (> or = 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Büsselberg
D
D
Heinrich Heine Universität Düsseldorf, Physiologisches Institut II, Germany.
Platt
B
B
Michael
D
D
Carpenter
D O
DO
Haas
H L
HL
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects*; D007854:Lead / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology*
D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels; D007854:Lead; D000535:Aluminum; D015032:Zinc