|
|
|
|
|
|
|
||
Article |
Molecular Interactions Involving the Inner Vestibule of the Pore
Kv4 channels represent the main class of brain A-type K+ channels that operate in the subthreshold range of membrane potentials (Serodio, P., E. Vega-Saenz de Miera, and B. Rudy. 1996. J. Neurophysiol. 75:2174– 2179), and their function depends critically on inactivation gating. A previous study suggested that the cytoplasmic NH2- and COOH-terminal domains of Kv4.1 channels act in concert to determine the fast phase of the complex time course of macroscopic inactivation (Jerng, H.H., and M. Covarrubias. 1997. Biophys. J. 72:163–174). To investigate the structural basis of slow inactivation gating of these channels, we examined internal residues that may affect the mutually exclusive relationship between inactivation and closed-state blockade by 4-aminopyridine (4-AP) (Campbell, D.L., Y. Qu, R.L. Rasmussen, and H.C. Strauss. 1993. J. Gen. Physiol. 101:603–626; Shieh, C.-C., and G.E. Kirsch. 1994. Biophys. J. 67:2316–2325). A double mutation V[404,406]I in the distal section of the S6 region of the protein drastically slowed channel inactivation and deactivation, and significantly reduced the blockade by 4-AP. In addition, recovery from inactivation was slightly faster, but the pore properties were not significantly affected. Consistent with a more stable open state and disrupted closed state inactivation, V[404,406]I also caused hyperpolarizing and depolarizing shifts of the peak conductance–voltage curve (
5 mV) and the prepulse inactivation curve (>10 mV), respectively. By contrast, the analogous mutations (V[556,558]I) in a K+ channel that undergoes N- and C-type inactivation (Kv1.4) did not affect macroscopic inactivation but dramatically slowed deactivation and recovery from inactivation, and eliminated open-channel blockade by 4-AP. Mutation of a Kv4-specifc residue in the S4–S5 loop (C322S) of Kv4.1 also altered gating and 4-AP sensitivity in a manner that closely resembles the effects of V[404,406]I. However, this mutant did not exhibit disrupted closed state inactivation. A kinetic model that assumes coupling between channel closing and inactivation at depolarized membrane potentials accounts for the results. We propose that components of the pore's internal vestibule control both closing and inactivation in Kv4 K+ channels.
Key Words: Shal channels • inactivation kinetics • A-type currents • 4-aminopyridine
Abbreviations: 4-AP, 4-aminopyridine; G/V, conductance–voltage; Kv channel, voltage-gated K+ channel
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Xie, V. E. Bondarenko, M. J. Morales, and H. C. Strauss Closed-state inactivation in Kv4.3 isoforms is differentially modulated by protein kinase C Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1236 - C1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Boland, M. M. Drzewiecki, G. Timoney, and E. Casey Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels Am J Physiol Cell Physiol, May 1, 2009; 296(5): C1003 - C1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. A. Kaulin, J. A. De Santiago-Castillo, C. A. Rocha, M. S. Nadal, B. Rudy, and M. Covarrubias The Dipeptidyl-Peptidase-Like Protein DPP6 Determines the Unitary Conductance of Neuronal Kv4.2 Channels J. Neurosci., March 11, 2009; 29(10): 3242 - 3251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Liang, H. Wang, H. Chen, Y. Cui, L. Gu, J. Chai, and K. Wang Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation J. Biol. Chem., February 20, 2009; 284(8): 4960 - 4967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Barghaan and R. Bahring Dynamic Coupling of Voltage Sensor and Gate Involved in Closed-State Inactivation of Kv4.2 Channels J. Gen. Physiol., February 1, 2009; 133(2): 205 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Jerng and P. J. Pfaffinger Multiple Kv Channel-interacting Proteins Contain an N-terminal Transmembrane Domain That Regulates Kv4 Channel Trafficking and Gating J. Biol. Chem., December 19, 2008; 283(51): 36046 - 36059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. C. L. Bett and R. L. Rasmusson Modification of K+ channel-drug interactions by ancillary subunits J. Physiol., February 15, 2008; 586(4): 929 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Cai and F. Sesti A New Mode of Regulation of N-type Inactivation in a Caenorhabditis elegans Voltage-gated Potassium Channel J. Biol. Chem., June 22, 2007; 282(25): 18597 - 18601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-L. Li, Y.-J. Qu, Y. C. Lu, V. E. Bondarenko, S. Wang, I. M. Skerrett, and M. J. Morales DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4 Am J Physiol Cell Physiol, November 1, 2006; 291(5): C966 - C976. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
H. H Jerng, K. Kunjilwar, and P. J Pfaffinger Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA-like properties J. Physiol., November 1, 2005; 568(3): 767 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T Kurata, K. W Doerksen, J. R Eldstrom, S. Rezazadeh, and D. Fedida Separation of P/C- and U-type inactivation pathways in Kv1.5 potassium channels J. Physiol., October 1, 2005; 568(1): 31 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. B. Winkelman, C. L. Beck, D. L. Ypey, and M. E. O'Leary Inhibition of the A-Type K+ Channels of Dorsal Root Ganglion Neurons by the Long-Duration Anesthetic Butamben J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1177 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zeng, T. M. Weiger, H. Fei, A. M. Jaramillo, and I. B. Levitan The Amino Terminus of Slob, Slowpoke Channel Binding Protein, Critically Influences Its Modulation of the Channel J. Gen. Physiol., May 31, 2005; 125(6): 631 - 640. [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]
|
|
|
|
|
|
X. Chen and D. Johnston Properties of single voltage-dependent K+ channels in dendrites of CA1 pyramidal neurones of rat hippocampus J. Physiol., August 15, 2004; 559(1): 187 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-H. Zhang, K. J. Rhodes, W. E. Childers, T. M. Argentieri, and Q. Wang "Disinactivation" of N-type Inactivation of Voltage-gated K Channels by an Erbstatin Analogue J. Biol. Chem., July 9, 2004; 279(28): 29226 - 29230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Birnbaum, A. W. Varga, L.-L. Yuan, A. E. Anderson, J. D. Sweatt, and L. A. Schrader Structure and Function of Kv4-Family Transient Potassium Channels Physiol Rev, July 1, 2004; 84(3): 803 - 833. [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]
|
|
|
|
 |
|
 D. Oliver, C.-C. Lien, M. Soom, T. Baukrowitz, P. Jonas, and B. Fakler Functional Conversion Between A-Type and Delayed Rectifier K+ Channels by Membrane Lipids Science, April 9, 2004; 304(5668): 265 - 270. [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]
|
|
|
|
|
|
E S L. Faber and P. Sah Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala J. Physiol., October 15, 2003; 552(2): 483 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Harris, A. R. Graber, and M. Covarrubias Allosteric modulation of a neuronal K+ channel by 1-alkanols is linked to a key residue in the activation gate Am J Physiol Cell Physiol, October 1, 2003; 285(4): C788 - C796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Boland, M. Jiang, S. Y. Lee, S. C. Fahrenkrug, M. T. Harnett, and S. M. O'Grady Functional properties of a brain-specific NH2-terminally spliced modulator of Kv4 channels Am J Physiol Cell Physiol, July 1, 2003; 285(1): C161 - C170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kerschensteiner, F. Monje, and M. Stocker Structural Determinants of the Regulation of the Voltage-gated Potassium Channel Kv2.1 by the Modulatory alpha -Subunit Kv9.3 J. Biol. Chem., May 9, 2003; 278(20): 18154 - 18161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Schrader, A. E. Anderson, A. Mayne, P. J. Pfaffinger, and J. D. Sweatt PKA Modulation of Kv4.2-Encoded A-Type Potassium Channels Requires Formation of a Supramolecular Complex J. Neurosci., December 1, 2002; 22(23): 10123 - 10133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P Patel, D. L Campbell, and H. C Strauss Elucidating KChIP effects on Kv4.3 inactivation and recovery kinetics with a minimal KChIP2 isoform J. Physiol., November 15, 2002; 545(1): 5 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J Beck, M. Bowlby, W F. An, K. J Rhodes, and M. Covarrubias Remodelling inactivation gating of Kv4 channels by KChIP1, a small-molecular-weight calcium-binding protein J. Physiol., February 1, 2002; 538(3): 691 - 706. [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]
|
|
|
|
|
|
T. Y. Nakamura, D. J. Pountney, A. Ozaita, S. Nandi, S. Ueda, B. Rudy, and W. A. Coetzee A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-currents PNAS, October 12, 2001; (2001) 221168498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Kurata, G. S. Soon, and D. Fedida Altered State Dependence of C-Type Inactivation in the Long and Short Forms of Human Kv1.5 J. Gen. Physiol., September 1, 2001; 118(3): 315 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bahring, L. M Boland, A. Varghese, M. Gebauer, and O. Pongs Kinetic analysis of open- and closed-state inactivation transitions in human Kv4.2 A-type potassium channels J. Physiol., August 15, 2001; 535(1): 65 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Holmqvist, J. Cao, M. H. Knoppers, M. E. Jurman, P. S. Distefano, K. J. Rhodes, Y. Xie, and W. F. An Kinetic Modulation of Kv4-Mediated A-Current by Arachidonic Acid Is Dependent on Potassium Channel Interacting Proteins J. Neurosci., June 15, 2001; 21(12): 4154 - 4161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. McAnelly and H. H. Zakon Coregulation of Voltage-Dependent Kinetics of Na+ and K+ Currents in Electric Organ J. Neurosci., May 1, 2000; 20(9): 3408 - 3414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Harris, M. Shahidullah, J. S. Ellingson, and M. Covarrubias General Anesthetic Action at an Internal Protein Site Involving the S4-S5 Cytoplasmic Loop of a Neuronal K+ Channel J. Biol. Chem., February 18, 2000; 275(7): 4928 - 4936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bahring, J. Dannenberg, H. C. Peters, T. Leicher, O. Pongs, and D. Isbrandt Conserved Kv4 N-terminal Domain Critical for Effects of Kv Channel-interacting Protein 2.2 on Channel Expression and Gating J. Biol. Chem., June 22, 2001; 276(26): 23888 - 23894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Nakamura, D. J. Pountney, A. Ozaita, S. Nandi, S. Ueda, B. Rudy, and W. A. Coetzee A role for frequenin, a Ca2+-binding protein, as a regulator of Kv4 K+-currents PNAS, October 23, 2001; 98(22): 12808 - 12813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhang, M. Jiang, and G.-N. Tseng MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating Function : Potential Role as {beta} Subunit of Cardiac Transient Outward Channel? Circ. Res., May 25, 2001; 88(10): 1012 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
