This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shahidullah, M. Articles by Covarrubias, M. Search for Related Content PubMed PubMed Citation Articles by Shahidullah, M. Articles by Covarrubias, M.

The Link between Ion Permeation and Inactivation Gating of Kv4 Potassium Channels

Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Correspondence: Address reprint requests to Manuel Covarrubias, Dept. of Pathology, Anatomy and Cell Biology, Jefferson Medical College of Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107. Tel.: 215-503-4341; Fax: 215-923-2218; E-mail: manuel.covarrubias{at}mail.tju.edu.

Kv4 potassium channels undergo rapid inactivation but do not seem to exhibit the classical N-type and C-type mechanisms present in other Kv channels. We have previously hypothesized that Kv4 channels preferentially inactivate from the preopen closed state, which involves regions of the channel that contribute to the internal vestibule of the pore. To further test this hypothesis, we have examined the effects of permeant ions on gating of three Kv4 channels (Kv4.1, Kv4.2, and Kv4.3) expressed in Xenopus oocytes. Rb⁺ is an excellent tool for this purpose because its prolonged residency time in the pore delays K⁺ channel closing. The data showed that, only when Rb⁺ carried the current, both channel closing and the development of macroscopic inactivation are slowed (1.5- to 4-fold, relative to the K⁺ current). Furthermore, macroscopic Rb⁺ currents were larger than K⁺ currents (1.2- to 3-fold) as the result of a more stable open state, which increases the maximum open probability. These results demonstrate that pore occupancy can influence inactivation gating in a manner that depends on how channel closing impacts inactivation from the preopen closed state. By examining possible changes in ionic selectivity and the influence of elevating the external K⁺ concentration, additional experiments did not support the presence of C-type inactivation in Kv4 channels.

This article has been cited by other articles:

				Y. Amarillo, J. A. De Santiago-Castillo, K. Dougherty, J. Maffie, E. Kwon, M. Covarrubias, and B. Rudy Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons J. Physiol., April 15, 2008; 586(8): 2093 - 2106. [Abstract] [Full Text] [PDF]

				Yu. A. Kaulin, J. A. De Santiago-Castillo, C. A. Rocha, and M. Covarrubias Mechanism of the Modulation of Kv4:KChIP-1 Channels by External K+ Biophys. J., February 15, 2008; 94(4): 1241 - 1251. [Abstract] [Full Text] [PDF]

				J. Barghaan, M. Tozakidou, H. Ehmke, and R. Bahring Role of N-Terminal Domain and Accessory Subunits in Controlling Deactivation-Inactivation Coupling of Kv4.2 Channels Biophys. J., February 15, 2008; 94(4): 1276 - 1294. [Abstract] [Full Text] [PDF]

				G. Wang and M. Covarrubias Voltage-dependent Gating Rearrangements in the Intracellular T1-T1 Interface of a K+ Channel J. Gen. Physiol., March 27, 2006; 127(4): 391 - 400. [Abstract] [Full Text] [PDF]

				S. P. Patel and D. L. Campbell Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms J. Physiol., November 15, 2005; 569(1): 7 - 39. [Abstract] [Full Text] [PDF]

				S. Wang, V. E. Bondarenko, Y.-j. Qu, G. C. L. Bett, M. J. Morales, R. L. Rasmusson, and H. C. Strauss Time- and Voltage-Dependent Components of Kv4.3 Inactivation Biophys. J., November 1, 2005; 89(5): 3026 - 3041. [Abstract] [Full Text] [PDF]

				G. Wang, M. Shahidullah, C. A. Rocha, C. Strang, P. J. Pfaffinger, and M. Covarrubias Functionally Active T1-T1 Interfaces Revealed by the Accessibility of Intracellular Thiolate Groups in Kv4 Channels J. Gen. Physiol., June 27, 2005; 126(1): 55 - 69. [Abstract] [Full Text] [PDF]

				S. Wang, V. E. Bondarenko, Y. Qu, M. J. Morales, R. L. Rasmusson, and H. C. Strauss Activation properties of Kv4.3 channels: time, voltage and [K+]o dependence J. Physiol., June 15, 2004; 557(3): 705 - 717. [Abstract] [Full Text] [PDF]

				M. Gebauer, D. Isbrandt, K. Sauter, B. Callsen, A. Nolting, O. Pongs, and R. Bahring N-type Inactivation Features of Kv4.2 Channel Gating Biophys. J., January 1, 2004; 86(1): 210 - 223. [Abstract] [Full Text] [PDF]