Biophys J, August 2001, p. 867-883, Vol. 81, No. 2

Kv4 Channels Exhibit Modulation of Closed-State Inactivation in Inside-Out Patches

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

The mechanisms of inactivation gating of the neuronal somatodendritic A-type K⁺ current and the cardiac I_to were investigated in Xenopus oocyte macropatches expressing Kv4.1 and Kv4.3 channels. Upon membrane patch excision (inside-out), Kv4.1 channels undergo time-dependent acceleration of macroscopic inactivation accompanied by a parallel partial current rundown. These changes are readily reversible by patch cramming, suggesting the influence of modulatory cytoplasmic factors. The consequences of these perturbations were investigated in detail to gain insights into the biophysical basis and mechanisms of inactivation gating. Accelerated inactivation at positive voltages (0 to +110 mV) is mainly the result of reducing the time constant of slow inactivation and the relative weight of the slow component of inactivation. Concomitantly, the time constants of closed-state inactivation at negative membrane potentials (90 to 50 mV) are substantially decreased in inside-out patches. Deactivation is moderately accelerated, and recovery from inactivation and the peak G-V curve exhibit little or no change. In agreement with more favorable closed-state inactivation in inside-out patches, the steady-state inactivation curve exhibits a hyperpolarizing shift of ~10 mV. Closed-state inactivation was similarly enhanced in Kv4.3. An allosteric model that assumes significant closed-state inactivation at all relevant voltages can explain Kv4 inactivation gating and the modulatory changes.

Biophys J, August 2001, p. 867-883, Vol. 81, No. 2
© 2001 by the Biophysical Society   0006-3495/01/08/867/17  $2.00

This article has been cited by other articles:

				O. Colinas, F. D. Perez-Carretero, J. R. Lopez-Lopez, and M. T. Perez-Garcia A Role for DPPX Modulating External TEA Sensitivity of Kv4 Channels J. Gen. Physiol., May 1, 2008; 131(5): 455 - 471. [Abstract] [Full Text] [PDF]

				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]

				K. Dougherty, J. A. De Santiago-Castillo, and M. Covarrubias Gating Charge Immobilization in Kv4.2 Channels: The Basis of Closed-State Inactivation J. Gen. Physiol., February 25, 2008; 131(3): 257 - 273. [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]

				D. Van Hoorick, A. Raes, and D. J. Snyders The aromatic cluster in KCHIP1b affects Kv4 inactivation gating J. Physiol., September 15, 2007; 583(3): 959 - 969. [Abstract] [Full Text] [PDF]

				A. Bhattacharji, B. Kaplan, T. Harris, X. Qu, M. W. Germann, and M. Covarrubias The Concerted Contribution of the S4-S5 Linker and the S6 Segment to the Modulation of a Kv Channel by 1-Alkanols Mol. Pharmacol., November 1, 2006; 70(5): 1542 - 1554. [Abstract] [Full Text] [PDF]

				H. S. Ahn, S. E. Kim, H.-J. Jang, M.-J. Kim, D.-J. Rhie, S.-H. Yoon, Y.-H. Jo, M.-S. Kim, K.-W. Sung, and S. J. Hahn Interaction of Riluzole with the Closed Inactivated State of Kv4.3 Channels J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 323 - 331. [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]

				D. V. Vasilyev, T. L. Merrill, and M. R. Bowlby Development of a Novel Automated Ion Channel Recording Method Using "Inside-Out" Whole-Cell Membranes J Biomol Screen, December 1, 2005; 10(8): 806 - 813. [Abstract] [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]

				K. Kunjilwar, C. Strang, D. DeRubeis, and P. J. Pfaffinger KChIP3 Rescues the Functional Expression of Shal Channel Tetramerization Mutants J. Biol. Chem., December 24, 2004; 279(52): 54542 - 54551. [Abstract] [Full Text] [PDF]

				H. H. Jerng, Y. Qian, and P. J. Pfaffinger Modulation of Kv4.2 Channel Expression and Gating by Dipeptidyl Peptidase 10 (DPP10) Biophys. J., October 1, 2004; 87(4): 2380 - 2396. [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]

				S. P. Patel, R. Parai, R. Parai, and D. L. Campbell Regulation of Kv4.3 voltage-dependent gating kinetics by KChIP2 isoforms J. Physiol., May 15, 2004; 557(1): 19 - 41. [Abstract] [Full Text] [PDF]

				N. Hatano, S. Ohya, K. Muraki, R. B. Clark, W. R. Giles, and Y. Imaizumi Two Arginines in the Cytoplasmic C-terminal Domain Are Essential for Voltage-dependent Regulation of A-type K+ Current in the Kv4 Channel Subfamily J. Biol. Chem., February 13, 2004; 279(7): 5450 - 5459. [Abstract] [Full Text] [PDF]

				Z. Wang, J. R. Eldstrom, J. Jantzi, E. D. Moore, and D. Fedida Increased focal Kv4.2 channel expression at the plasma membrane is the result of actin depolymerization Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H749 - H759. [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]

				M. Shahidullah and M. Covarrubias The Link between Ion Permeation and Inactivation Gating of Kv4 Potassium Channels Biophys. J., February 1, 2003; 84(2): 928 - 941. [Abstract] [Full Text] [PDF]

				M. H. Holmqvist, J. Cao, R. Hernandez-Pineda, M. D. Jacobson, K. I. Carroll, M. A. Sung, M. Betty, P. Ge, K. J. Gilbride, M. E. Brown, et al. Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain PNAS, January 22, 2002; 99(2): 1035 - 1040. [Abstract] [Full Text] [PDF]