Divalent metals differentially block cloned T-type calcium channels

Neuroreport. 2003 Aug 6;14(11):1537-40. doi: 10.1097/00001756-200308060-00028.


We tested divalent metals including Cu2+, Pb2+, and Zn2+ to determine their pharmacological profiles for blockade of cloned T-type Ca2+ channels (alpha1G, alpha1 H, and alpha1I). Effects of the metals were also evaluated for native low and high voltage-activated Ca2+ channels in rat sympathetic pelvic neurons. Cu2+ and Zn2+ blocked three T-type channel isoforms in a concentration-dependent manner with a higher affinity for alpha1H currents (IC50 = 0.9 microM and 2.3 microM). In pelvic neurons, only Zn2+ showed strong selectivity for T-type Ca2+ currents over high voltage-activated Ca2+ currents. Conversely, Pb2+ block on Ca2+ channels did not show distinctive selectivity. Taken together, these results suggest that besides Ni2+, Cu2+ and Zn2+ can be used as selective blockers of alpha1 H at low concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channel Blockers*
  • Calcium Channels, T-Type / drug effects*
  • Calcium Channels, T-Type / genetics
  • Cations, Divalent / pharmacology*
  • Cell Line
  • Cloning, Molecular
  • Electrophysiology
  • Evoked Potentials / drug effects
  • Humans
  • Neurons / drug effects
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / drug effects


  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Cations, Divalent