| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received May 31, 2006
Revised July 10, 2006
Accepted after revision October 24, 2006
1 IGF CNRS UMR-5203
2 CNRS UMR5017 - U. Bordeaux II
* To whom correspondence should be addressed. E-mail: philippe.lory{at}igf.cnrs.fr.
Zinc (Zn2+) functions as a signalling molecule in the nervous system and modulates many ionic channels. In this study, we have explored the effects of Zn2+ on recombinant T-type calcium channels (CaV3.1, CaV3.2 and CaV3.3). Using tsA-201 cells, we demonstrate that CaV3.2 current (IC50 ~ 0.8 µM) is significantly more sensitive to Zn2+ than are CaV3.1 and CaV3.3 currents (IC50 ~ 80 µM and ~160 µM, respectively). This inhibition of CaV3 currents is associated with a shift to more negative membrane potentials of both steady-state inactivation for CaV3.1, CaV3.2 and CaV3.3 and steady-state activation for CaV3.1 and CaV3.3 currents. We also document changes in kinetics, especially a significant slowing of the inactivation kinetics for CaV3.1 and CaV3.3, but not for CaV3.2 currents. Notably, deactivation kinetics are significantly slowed for CaV3.3 current (~100 fold), but not for CaV3.1 and CaV3.2 currents. Consequently, application of Zn2+ results in a significant increase in CaV3.3 current in action potential clamp experiments, while CaV3.1 and CaV3.2 currents are significantly reduced. In neuroblastoma NG 108-15 cells, the duration of CaV3.3- mediated action potentials is increased upon Zn2+ application, indicating further that Zn2+ behaves as a CaV3.3 channel opener. These results demonstrate that Zn2+ exhibits differential modulatory effects on T-type calcium channels, which may partly explain the complex features of Zn2+ modulation of the neuronal excitability in normal and disease states.
This article has been cited by other articles:
|
|
 |
|
  H. R. Ross, I. Napier, and M. Connor Inhibition of Recombinant Human T-type Calcium Channels by {Delta}9-Tetrahydrocannabinol and Cannabidiol J. Biol. Chem., June 6, 2008; 283(23): 16124 - 16134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Nelson, P. M. Joksovic, P. Su, H.-W. Kang, A. Van Deusen, J. P. Baumgart, L. S. David, T. P. Snutch, P. Q. Barrett, J.-H. Lee, et al. Molecular Mechanisms of Subtype-Specific Inhibition of Neuronal T-Type Calcium Channels by Ascorbate J. Neurosci., November 14, 2007; 27(46): 12577 - 12583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cataldi, V. Lariccia, V. Marzaioli, A. Cavaccini, G. Curia, D. Viggiano, L.M.T. Canzoniero, G. di Renzo, M. Avoli, and L. Annunziato Zn2+ Slows Down CaV3.3 Gating Kinetics: Implications for Thalamocortical Activity J Neurophysiol, October 1, 2007; 98(4): 2274 - 2284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Sun, K. Hui, D. W. K. Lee, and Z.-P. Feng Zn2+ Sensitivity of High- and Low-Voltage Activated Calcium Channels Biophys. J., August 15, 2007; 93(4): 1175 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Nelson, J. Woo, H.-W. Kang, I. Vitko, P. Q. Barrett, E. Perez-Reyes, J.-H. Lee, H.-S. Shin, and S. M. Todorovic Reducing Agents Sensitize C-Type Nociceptors by Relieving High-Affinity Zinc Inhibition of T-Type Calcium Channels J. Neurosci., August 1, 2007; 27(31): 8250 - 8260. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
