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Nickel Block of Three Cloned T-Type Calcium Channels: Low Concentrations Selectively Block α1H

Published on Dec 1, 1999in Biophysical Journal3.67
· DOI :10.1016/S0006-3495(99)77134-1
Jung-Ha Lee9
Estimated H-index: 9
(Loyola University Medical Center),
Juan Carlos Gomora2
Estimated H-index: 2
(Loyola University Medical Center)
+ 1 AuthorsEdward Perez-Reyes57
Estimated H-index: 57
(Loyola University Medical Center)
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Abstract
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.
  • References (46)
  • Citations (462)
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References46
Newest
#1Edmund M. Talley (UVA: University of Virginia)H-Index: 29
#2Leanne L. Cribbs (Loyola University Medical Center)H-Index: 33
Last.Douglas A. Bayliss (UVA: University of Virginia)H-Index: 63
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#1Jung-Ha Lee (Loyola University Medical Center)H-Index: 9
#2Asif N. Daud (Loyola University Medical Center)H-Index: 10
Last.Edward Perez-Reyes (Loyola University Medical Center)H-Index: 57
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#1Jung-Ha Lee (Loyola University Medical Center)H-Index: 9
#2Leanne L. Cribbs (Loyola University Medical Center)H-Index: 33
Last.Edward Perez-Reyes (Loyola University Medical Center)H-Index: 57
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#1Norbert Klugbauer (LMU: Ludwig Maximilian University of Munich)H-Index: 18
#2Lubica Lacinová (LMU: Ludwig Maximilian University of Munich)H-Index: 8
Last.Franz Hofmann (LMU: Ludwig Maximilian University of Munich)H-Index: 88
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#1Rosalind S-I. Chuang (NIH: National Institutes of Health)H-Index: 1
#2Howard Jaffe (NIH: National Institutes of Health)H-Index: 34
Last.Kenton J. Swartz (NIH: National Institutes of Health)H-Index: 36
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#1Edward Perez-Reyes (Loyola University Medical Center)H-Index: 57
#2Leanne L. Cribbs (Loyola University Medical Center)H-Index: 33
Last.Jung-Ha Lee (Loyola University Medical Center)H-Index: 9
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#1Emilio Román Mustafa (UNLP: National University of La Plata)H-Index: 2
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#1Beth A. McNally (UMB: University of Maryland, Baltimore)H-Index: 2
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#2Laura Solé (CSU: Colorado State University)
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#1Kai Lyu (Nanjing Normal University)H-Index: 7
#2Xuan Wang (Nanjing Normal University)
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