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Biophys J, December 1999, p. 3034-3042, Vol. 77, No. 6
1H
Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153 USA
Nickel has been proposed to be a selective blocker of
low-voltage-activated, T-type calcium channels. However, studies on cloned high-voltage-activated Ca2+ channels indicated that
some subtypes, such as
1E, are also blocked by low micromolar
concentrations of NiCl2. There are considerable differences
in the sensitivity to Ni2+ 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
Ca2+ channels,
1G, 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 Ba2+). Only
1H currents were sensitive to low
micromolar concentrations (IC50 = 13 µM). Much
higher concentrations were required to half-block
1I (216 µM) and
1G currents (250 µM). 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 Ni2+ is only a selective
blocker of
1H currents and that the concentrations required to block
1G and
1I will also affect high-voltage-activated calcium currents.
Biophys J, December 1999, p. 3034-3042, Vol. 77, No. 6
© 1999 by the Biophysical Society 0006-3495/99/12/3034/09 $2.00
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