Circulation Research. 2001;88:1012-1019
Published online before print May 10, 2001, doi: 10.1161/hh1001.090839
Published online before print May 10, 2001, doi: 10.1161/hh1001.090839
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Molecular Medicine |
MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating Function
Potential Role as ß Subunit of Cardiac Transient Outward Channel?
From the Department of Physiology, Virginia Commonwealth University, Richmond, Va.
Correspondence to Gea-Ny Tseng, PhD, Department of Physiology, Virginia Commonwealth University, Richmond, VA 23298. E-mail gtseng{at}hsc.vcu.edu
Abstract—Inherited
mutations and a polymorphism in minK-related peptide 1 (MiRP1) have
been linked to congenital or acquired long-QT syndrome, pointing to the
importance of MiRP1 in maintaining the cardiac electrical stability. We
tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3),
the major pore-forming (
) subunits of transient outward
(Ito)
channels in the heart. We used the
Xenopus oocyte expression
system to examine the effects of MiRP1 on Kv4.x channel gating kinetics
and current amplitude and correlated these effects with MiRP1
expression level. MiRP1 slowed the rates of Kv4.2 activation and
inactivation and shifted the voltage dependence of channel gating in
the positive direction. These effects had a similar "dose"
dependence: they plateaued at a cRNA ratio (MiRP1:Kv4.2) of 13:1, with
half-maximum effects at estimated cRNA ratios of 2 to 4. On the other
hand, MiRP1 had no significant effects on Kv4.2 current amplitude in
the same range of expression level. When expressed at a comparable low
level, MiRP1 had similar (although smaller) effects on Kv4.3 but could
not modulate Kv1.4 (another subunit of
Ito
channels in the heart). Kv4.2 could be coimmunoprecipitated with
epitope-tagged MiRP1, indicating that the 2 could form a stable
complex. Our data suggest that MiRP1 may serve as a regulatory (ß)
subunit of
Ito
channels in the heart. This is supported by the observation that MiRP1
induced an "overshoot" of Kv4.2 current amplitude during channel
recovery from inactivation, similar to the overshoot of
Ito
described for human epicardial myocytes.
Key Words: Kv channel ß subunits • long QT • rapid component of delayed rectifier channels • transient outward channels • Xenopus oocytes
This article has been cited by other articles:
 |
|
 |
|
  M. Biel, C. Wahl-Schott, S. Michalakis, and X. Zong Hyperpolarization-Activated Cation Channels: From Genes to Function Physiol Rev, July 1, 2009; 89(3): 847 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Brandt, J. Endres-Becker, N. Zagidullin, L. J. Motloch, F. Er, D. Rottlaender, G. Michels, S. Herzig, and U. C. Hoppe Effects of KCNE2 on HCN isoforms: distinct modulation of membrane expression and single channel properties Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H355 - H363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jiang, X. Xu, Y. Wang, F. Toyoda, X.-S. Liu, M. Zhang, R. B. Robinson, and G.-N. Tseng Dynamic Partnership between KCNQ1 and KCNE1 and Influence on Cardiac IKs Current Amplitude by KCNE2 J. Biol. Chem., June 12, 2009; 284(24): 16452 - 16462. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. Maffie and B. Rudy Weighing the evidence for a ternary protein complex mediating A-type K+ currents in neurons J. Physiol., December 1, 2008; 586(23): 5609 - 5623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Roepke, A. Kontogeorgis, C. Ovanez, X. Xu, J. B. Young, K. Purtell, P. A. Goldstein, D. J. Christini, N. S. Peters, F. G. Akar, et al. Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f FASEB J, October 1, 2008; 22(10): 3648 - 3660. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. Panaghie and G. W. Abbott The Role of S4 Charges in Voltage-dependent and Voltage-independent KCNQ1 Potassium Channel Complexes J. Gen. Physiol., January 29, 2007; 129(2): 121 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Chandrasekhar, T. Bas, and W. R. Kobertz KCNE1 Subunits Require Co-assembly with K+ Channels for Efficient Trafficking and Cell Surface Expression J. Biol. Chem., December 29, 2006; 281(52): 40015 - 40023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Flaim, W. R. Giles, and A. D. McCulloch Contributions of sustained INa and IKv43 to transmural heterogeneity of early repolarization and arrhythmogenesis in canine left ventricular myocytes Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2617 - H2629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Radicke, D. Cotella, E. M. Graf, U. Banse, N. Jost, A. Varro, G.-N. Tseng, U. Ravens, and E. Wettwer Functional modulation of the transient outward current Ito by KCNE {beta}-subunits and regional distribution in human non-failing and failing hearts Cardiovasc Res, September 1, 2006; 71(4): 695 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Roepke, A. Anantharam, P. Kirchhoff, S. M. Busque, J. B. Young, J. P. Geibel, D. J. Lerner, and G. W. Abbott The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion J. Biol. Chem., August 18, 2006; 281(33): 23740 - 23747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, S. Y. Um, and T. V. Mcdonald Voltage-Gated Potassium Channels: Regulation by Accessory Subunits Neuroscientist, June 1, 2006; 12(3): 199 - 210. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Jespersen, M. Grunnet, and S.-P. Olesen The KCNQ1 Potassium Channel: From Gene to Physiological Function Physiology, December 1, 2005; 20(6): 408 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. H. Yu, V. Yarov-Yarovoy, G. A. Gutman, and W. A. Catterall Overview of Molecular Relationships in the Voltage-Gated Ion Channel Superfamily Pharmacol. Rev., December 1, 2005; 57(4): 387 - 395. [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]
|
|
|
|
|
|
J. M. Nerbonne and R. S. Kass Molecular Physiology of Cardiac Repolarization Physiol Rev, October 1, 2005; 85(4): 1205 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Nie, M. A. Gratton, K. J. Mu, J. N. Dinglasan, W. Feng, and E. N. Yamoah Expression and Functional Phenotype of Mouse ERG K+ Channels in the Inner Ear: Potential Role in K+ Regulation in the Inner Ear J. Neurosci., September 21, 2005; 25(38): 8671 - 8679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bendahhou, C. Marionneau, K. Haurogne, M.-M. Larroque, R. Derand, V. Szuts, D. Escande, S. Demolombe, and J. Barhanin In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart Cardiovasc Res, August 15, 2005; 67(3): 529 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Duzhyy, M. Harvey, and B. Sokolowski A Secretory-type Protein, Containing a Pentraxin Domain, Interacts with an A-type K+ Channel J. Biol. Chem., April 15, 2005; 280(15): 15165 - 15172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Aimond, S. P. Kwak, K. J. Rhodes, and J. M. Nerbonne Accessory Kv{beta}1 Subunits Differentially Modulate the Functional Expression of Voltage-Gated K+ Channels in Mouse Ventricular Myocytes Circ. Res., March 4, 2005; 96(4): 451 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Gage and W. R. Kobertz KCNE3 Truncation Mutants Reveal a Bipartite Modulation of KCNQ1 K+ Channels J. Gen. Physiol., November 29, 2004; 124(6): 759 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Qu, Y. Kryukova, I. A. Potapova, S. V. Doronin, M. Larsen, G. Krishnamurthy, I. S. Cohen, and R. B. Robinson MiRP1 Modulates HCN2 Channel Expression and Gating in Cardiac Myocytes J. Biol. Chem., October 15, 2004; 279(42): 43497 - 43502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. H. Yu and W. A. Catterall The VGL-Chanome: A Protein Superfamily Specialized for Electrical Signaling and Ionic Homeostasis Sci. Signal., October 5, 2004; 2004(253): re15 - re15. [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]
|
|
|
|
 |
|
 M. Jiang, M. Zhang, D. G. Tang, H. F. Clemo, J. Liu, D. Holwitt, V. Kasirajan, A. L. Pond, E. Wettwer, and G.-N. Tseng KCNE2 Protein Is Expressed in Ventricles of Different Species, and Changes in Its Expression Contribute to Electrical Remodeling in Diseased Hearts Circulation, April 13, 2004; 109(14): 1783 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lewis, Z. A. McCrossan, and G. W. Abbott MinK, MiRP1, and MiRP2 Diversify Kv3.1 and Kv3.2 Potassium Channel Gating J. Biol. Chem., February 27, 2004; 279(9): 7884 - 7892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wong and L. C. Schlichter Differential Recruitment of Kv1.4 and Kv4.2 to Lipid Rafts by PSD-95 J. Biol. Chem., January 2, 2004; 279(1): 444 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sternberg, N. Tabti, E. Fournier, B. Hainque, and B. Fontaine Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis Neurology, September 23, 2003; 61(6): 857 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. A. McCrossan, A. Lewis, G. Panaghie, P. N. Jordan, D. J. Christini, D. J. Lerner, and G. W. Abbott MinK-Related Peptide 2 Modulates Kv2.1 and Kv3.1 Potassium Channels in Mammalian Brain J. Neurosci., September 3, 2003; 23(22): 8077 - 8091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lu, M. P Mahaut-Smith, C. L-H Huang, and J. I Vandenberg Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6 J. Physiol., August 15, 2003; 551(1): 253 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pourrier, S. Zicha, J. Ehrlich, W. Han, and S. Nattel Canine Ventricular KCNE2 Expression Resides Predominantly in Purkinje Fibers Circ. Res., August 8, 2003; 93(3): 189 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Anantharam, A. Lewis, G. Panaghie, E. Gordon, Z. A. McCrossan, D. J. Lerner, and G. W. Abbott RNA Interference Reveals That Endogenous Xenopus MinK-related Peptides Govern Mammalian K+ Channel Function in Oocyte Expression Studies J. Biol. Chem., March 28, 2003; 278(14): 11739 - 11745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bianchi, S.-M. Kwok, M. Driscoll, and F. Sesti A Potassium Channel-MiRP Complex Controls Neurosensory Function in Caenorhabditis elegans J. Biol. Chem., March 28, 2003; 278(14): 12415 - 12424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C Amberg, S. D. Koh, W. J Hatton, K. J Murray, K. Monaghan, B. Horowitz, and K. M Sanders Contribution of Kv4 channels toward the A-type potassium current in murine colonic myocytes J. Physiol., October 15, 2002; 544(2): 403 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C Amberg, S. A Baker, S. D. Koh, W. J Hatton, K. J Murray, B. Horowitz, and K. M Sanders Characterization of the A-type potassium current in murine gastric antrum J. Physiol., October 15, 2002; 544(2): 417 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takimoto, E.-K. Yang, and L. Conforti Palmitoylation of KChIP Splicing Variants Is Required for Efficient Cell Surface Expression of Kv4.3 Channels J. Biol. Chem., July 19, 2002; 277(30): 26904 - 26911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, S. A. Malin, D. C. Johns, A. Jeromin, and J. M. Nerbonne Modulation of Kv4-encoded K+ Currents in the Mammalian Myocardium by Neuronal Calcium Sensor-1 J. Biol. Chem., July 12, 2002; 277(29): 26436 - 26443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. F. Melman, A. Krumerman, and T. V. McDonald A Single Transmembrane Site in the KCNE-encoded Proteins Controls the Specificity of KvLQT1 Channel Gating J. Biol. Chem., July 5, 2002; 277(28): 25187 - 25194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grunnet, T. Jespersen, H. B. Rasmussen, T. Ljungstrom, N. K Jorgensen, S.-P. Olesen, and D. A Klaerke KCNE4 is an inhibitory subunit to the KCNQ1 channel J. Physiol., July 1, 2002; 542(1): 119 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weerapura, S. Nattel, D. Chartier, R. Caballero, and T. E Hebert A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link? J. Physiol., April 1, 2002; 540(1): 15 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P Patel, D. L Campbell, M. J Morales, and H. C Strauss Heterogeneous expression of KChIP2 isoforms in the ferret heart J. Physiol., March 15, 2002; 539(3): 649 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. ABBOTT and S. A. N. GOLDSTEIN Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism FASEB J, March 1, 2002; 16(3): 390 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Proenza, D. Angoli, E. Agranovich, V. Macri, and E. A. Accili Pacemaker Channels Produce an Instantaneous Current J. Biol. Chem., February 8, 2002; 277(7): 5101 - 5109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S Nadal, Y. Amarillo, E. V.-S. de Miera, and B. Rudy Evidence for the presence of a novel Kv4-mediated A-type K+ channel-modifying factor J. Physiol., December 15, 2001; 537(3): 801 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Nerbonne, C. G. Nichols, T. L. Schwarz, and D. Escande Genetic Manipulation of Cardiac K+ Channel Function in Mice: What Have We Learned, and Where Do We Go From Here? Circ. Res., November 23, 2001; 89(11): 944 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Abbott and S. A. N. Goldstein Potassium Channel Subunits: The MiRP Family Mol. Interv., June 1, 2001; 1(2): 95 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Abbott, S. A. N. Goldstein, and F. Sesti Do All Voltage-Gated Potassium Channels Use MiRPs? Circ. Res., May 25, 2001; 88(10): 981 - 983. [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. Weerapura, S. Nattel, D. Chartier, R. Caballero, and T. E Hebert A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link? J. Physiol., April 1, 2002; 540(1): 15 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S Nadal, Y. Amarillo, E. V.-S. de Miera, and B. Rudy Evidence for the presence of a novel Kv4-mediated A-type K+ channel-modifying factor J. Physiol., December 15, 2001; 537(3): 801 - 809. [Abstract] [Full Text] [PDF]
|
|