Nickel block of three cloned T-type calcium channels: low concentrations selectively block alpha1H

Biophys J. 1999 Dec;77(6):3034-42. doi: 10.1016/S0006-3495(99)77134-1.


Nickel has been proposed to be a selective blocker of low-voltage-activated, T-type calcium channels. However, studies on cloned high-voltage-activated Ca(2+) channels indicated that some subtypes, such as alpha1E, are also blocked by low micromolar concentrations of NiCl(2). There are considerable differences in the sensitivity to Ni(2+) among native T-type currents, leading to the hypothesis that there may be more than one T-type channel. We confirmed part of this hypothesis by cloning three novel Ca(2+) channels, alpha1G, H, and I, whose currents are nearly identical to the biophysical properties of native T-type channels. In this study we examined the nickel block of these cloned T-type channels expressed in both Xenopus oocytes and HEK-293 cells (10 mM Ba(2+)). Only alpha1H currents were sensitive to low micromolar concentrations (IC(50) = 13 microM). Much higher concentrations were required to half-block alpha1I (216 microM) and alpha1G currents (250 microM). Nickel block varied with the test potential, with less block at potentials above -30 mV. Outward currents through the T channels were blocked even less. We show that depolarizations can unblock the channel and that this can occur in the absence of permeating ions. We conclude that Ni(2+) is only a selective blocker of alpha1H currents and that the concentrations required to block alpha1G and alpha1I will also affect high-voltage-activated calcium currents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biophysical Phenomena
  • Biophysics
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, T-Type / drug effects*
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / metabolism
  • Cell Line
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • In Vitro Techniques
  • Membrane Potentials
  • Nickel / administration & dosage
  • Nickel / pharmacology*
  • Oocytes / metabolism
  • Rats
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection
  • Xenopus laevis


  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Recombinant Proteins
  • Nickel