© 1995 American Heart Association, Inc.
Articles |
Differential Expression of Voltage-Gated K+ Channel Subunits in Adult Rat Heart
Relation to Functional K+ Channels?
From the Department of Molecular Biology and Pharmacology (D.M.B., J.P.M., J.M.N.), Washington University School of Medicine, St Louis, Mo, and the Department of Biochemistry and Cell Biology (J.S.T.), State University of New York at Stonybrook.
Correspondence to Dr Jeanne M. Nerbonne, Department of Molecular Biology and Pharmacology, Box 8103, Washington University School of Medicine, 660 South Euclid Ave, St Louis, MO 63110. E-mail jnerbonn@pharmdec.wustl.edu.
Abstract Polyclonal antibodies against each of the K+ channel subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) shown previously to be expressed in adult rat heart at the mRNA level were used to examine the distributions of these K+ channel subunits in adult rat atrial and ventricular membranes. Immunohistochemistry on isolated adult rat ventricular myocytes revealed strong labeling with the anti-Kv4.2 and anti-Kv1.2 antibodies. Although somewhat weaker (than with anti-Kv1.2 or anti-Kv4.2), positive staining was also observed with the anti-Kv1.5 and anti-Kv2.1 antibodies. Ventricular myocytes exposed to the anti-Kv1.4 antibody, in contrast, did not appear significantly different from background. Qualitatively similar results were obtained on isolated adult rat atrial myocytes. Western blots of atrial and ventricular membrane proteins confirmed the presence of Kv1.2, Kv1.5, Kv2.1, and Kv4.2 and revealed differences in the relative abundances of these subunits in the two membrane preparations. Kv4.2, for example, is more abundant in ventricular than in atrial membranes, whereas Kv1.2 and Kv2.1 are higher in atrial membranes; Kv1.5 levels are comparable in the two preparations. In contrast to these results, nothing was detected in Western blots of atrial or ventricular membrane proteins with the anti-Kv1.4 antibody at concentrations that revealed intense labeling of a 97-kD protein in adult rat brain membranes. A very faint band was detected at 97 kD in the atrial and ventricular preparations when the anti-Kv1.4 antibody was used at a 5- to 10-fold higher concentration. The simplest interpretation of these results is that Kv1.4 is not an abundant protein in adult rat atrial or ventricular myocytes. Therefore, it seems unlikely that Kv1.4 plays an important role in the formation of functional depolarization-activated K+ channels in these cells. The relation(s) between the (other four) K+ channel subunits and the depolarization-activated K+ channels identified electrophysiologically in adult rat atrial and ventricular myocytes is discussed in the present study.
Key Words: depolarization-activated K+ channels • Shaker • Shab • Shal • cardiac myocytes
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H. M. Himmel, E. Wettwer, Q. Li, and U. Ravens Four different components contribute to outward current in rat ventricular myocytes Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H107 - H118. [Abstract] [Full Text] [PDF]
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E. Bou-Abboud and J. M Nerbonne Molecular correlates of the calcium-independent, depolarization-activated K+ currents in rat atrial myocytes J. Physiol., June 1, 1999; 517(2): 407 - 420. [Abstract] [Full Text] [PDF]
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H. Xu, W. Guo, and J. M. Nerbonne Four Kinetically Distinct Depolarization-activated K+ Currents in Adult Mouse Ventricular Myocytes J. Gen. Physiol., May 1, 1999; 113(5): 661 - 678. [Abstract] [Full Text] [PDF]
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J. V. Steidl and A. J. Yool Differential Sensitivity of Voltage-Gated Potassium Channels Kv1.5 and Kv1.2 to Acidic pH and Molecular Identification of pH Sensor Mol. Pharmacol., May 1, 1999; 55(5): 812 - 820. [Abstract] [Full Text]
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A. D. Wickenden, T. J. Jegla, R. Kaprielian, and P. H. Backx Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1599 - H1607. [Abstract] [Full Text] [PDF]
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D. J Snyders Structure and function of cardiac potassium channels Cardiovasc Res, May 1, 1999; 42(2): 377 - 390. [Abstract] [Full Text] [PDF]
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L. Yue, P. Melnyk, R. Gaspo, Z. Wang, and S. Nattel Molecular Mechanisms Underlying Ionic Remodeling in a Dog Model of Atrial Fibrillation Circ. Res., April 16, 1999; 84(7): 776 - 784. [Abstract] [Full Text] [PDF]
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M. V. Brahmajothi, D. L. Campbell, R. L. Rasmusson, M. J. Morales, J. S. Trimmer, J. M. Nerbonne, and H. C. Strauss Distinct Transient Outward Potassium Current (Ito) Phenotypes and Distribution of Fast-inactivating Potassium Channel Alpha Subunits in Ferret Left Ventricular Myocytes J. Gen. Physiol., April 1, 1999; 113(4): 581 - 600. [Abstract] [Full Text] [PDF]
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Z. Wang, J. Feng, H. Shi, A. Pond, J. M. Nerbonne, and S. Nattel Potential Molecular Basis of Different Physiological Properties of the Transient Outward K+ Current in Rabbit and Human Atrial Myocytes Circ. Res., March 19, 1999; 84(5): 551 - 561. [Abstract] [Full Text] [PDF]
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D. McKinnon Molecular Identity of Ito : Kv1.4 Redux Circ. Res., March 19, 1999; 84(5): 620 - 622. [Full Text] [PDF]
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H. Murakoshi and J. S. Trimmer Identification of the Kv2.1 K+ Channel as a Major Component of the Delayed Rectifier K+ Current in Rat Hippocampal Neurons J. Neurosci., March 1, 1999; 19(5): 1728 - 1735. [Abstract] [Full Text] [PDF]
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D. Fedida, N. D Maruoka, and S. Lin Modulation of slow inactivation in human cardiac Kv1.5 channels by extra- and intracellular permeant cations J. Physiol., March 1, 1999; 515(2): 315 - 329. [Abstract] [Full Text] [PDF]
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K. Petrecca, R. Atanasiu, S. Grinstein, J. Orlowski, and A. Shrier Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H709 - H717. [Abstract] [Full Text] [PDF]
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W. Guo, K. Kamiya, K. Yasui, I. Kodama, and J. Toyama Paracrine hypertrophic factors from cardiac non-myocyte cells downregulate the transient outward current density and Kv4.2 K+ channel expression in cultured rat cardiomyocytes Cardiovasc Res, January 1, 1999; 41(1): 157 - 165. [Abstract] [Full Text] [PDF]
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J.-F. Faivre, T. P.G. Calmels, S. Rouanet, J.-L. Javre, B. Cheval, and A. Bril Characterisation of Kv4.3 in HEK293 cells: comparison with the rat ventricular transient outward potassium current Cardiovasc Res, January 1, 1999; 41(1): 188 - 199. [Abstract] [Full Text] [PDF]
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L. Franqueza, C. Valenzuela, J. Eck, M.M. Tamkun, J. Tamargo, and D.J. Snyders Functional expression of an inactivating potassium channel (Kv4.3) in a mammalian cell line Cardiovasc Res, January 1, 1999; 41(1): 212 - 219. [Abstract] [Full Text] [PDF]
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Z. Wang, L. Yue, M. White, G. Pelletier, and S. Nattel Differential Distribution of Inward Rectifier Potassium Channel Transcripts in Human Atrium Versus Ventricle Circulation, December 1, 1998; 98(22): 2422 - 2428. [Abstract] [Full Text] [PDF]
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L. M. Pacioretty and R. F. Gilmour Jr. Restoration of transient outward current by norepinephrine in cultured canine cardiac myocytes Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1599 - H1605. [Abstract] [Full Text] [PDF]
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A. Nishiyama, F. Kambe, K. Kamiya, H. Seo, and J. Toyama Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle Cardiovasc Res, November 1, 1998; 40(2): 343 - 351. [Abstract] [Full Text] [PDF]
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J. Zhou, A. Jeron, B. London, X. Han, and G. Koren Characterization of a Slowly Inactivating Outward Current in Adult Mouse Ventricular Myocytes Circ. Res., October 19, 1998; 83(8): 806 - 814. [Abstract] [Full Text] [PDF]
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S. Kaab, J. Dixon, J. Duc, D. Ashen, M. Nabauer, D. J. Beuckelmann, G. Steinbeck, D. McKinnon, and G. F. Tomaselli Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure : A Decrease in Kv4.3 mRNA Correlates With a Reduction in Current Density Circulation, October 6, 1998; 98(14): 1383 - 1393. [Abstract] [Full Text] [PDF]
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D. M. Barry, H. Xu, R. B. Schuessler, and J. M. Nerbonne Functional Knockout of the Transient Outward Current, Long-QT Syndrome, and Cardiac Remodeling in Mice Expressing a Dominant-Negative Kv4 {alpha} Subunit Circ. Res., September 7, 1998; 83(5): 560 - 567. [Abstract] [Full Text] [PDF]
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R.-L. Wu, D. M. Butler, and M. E. Barish Potassium Current Development and its Linkage to Membrane Expansion During Growth of Cultured Embryonic Mouse Hippocampal Neurons: Sensitivity to Inhibitors of Phosphatidylinositol 3-Kinase and Other Protein Kinases J. Neurosci., August 15, 1998; 18(16): 6261 - 6278. [Abstract] [Full Text] [PDF]
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B. London, D. W Wang, J. A Hill, and P. B Bennett The transient outward current in mice lacking the potassium channel gene Kv1.4 J. Physiol., May 15, 1998; 509(1): 171 - 182. [Abstract] [Full Text] [PDF]
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R. L. Rasmusson, M. J. Morales, S. Wang, S. Liu, D. L. Campbell, M. V. Brahmajothi, and H. C. Strauss Inactivation of Voltage-Gated Cardiac K+ Channels Circ. Res., April 20, 1998; 82(7): 739 - 750. [Abstract] [Full Text] [PDF]
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 X.-J. Yuan, J. Wang, M. Juhaszova, V. A. Golovina, and L. J. Rubin Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 1998; 274(4): L621 - L635. [Abstract] [Full Text] [PDF]
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D. C. Johns, H. B. Nuss, and E. Marban Suppression of Neuronal and Cardiac Transient Outward Currents by Viral Gene Transfer of Dominant-Negative Kv4.2 Constructs J. Biol. Chem., December 12, 1997; 272(50): 31598 - 31603. [Abstract] [Full Text] [PDF]
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H.-S. Wang, J. E. Dixon, and D. McKinnon Unexpected and Differential Effects of Cl- Channel Blockers on the Kv4.3 and Kv4.2 K+ Channels : Implications for the Study of the Ito2 Current Circ. Res., November 19, 1997; 81(5): 711 - 718. [Abstract] [Full Text]
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K. Takimoto, D. Li, K. M. Hershman, P. Li, E. K. Jackson, and E. S. Levitan Decreased Expression of Kv4.2 and Novel Kv4.3 K+ Channel Subunit mRNAs in Ventricles of Renovascular Hypertensive Rats Circ. Res., October 19, 1997; 81(4): 533 - 539. [Abstract] [Full Text]
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T. Y. Nakamura, W. A. Coetzee, E. Vega-Saenz De Miera, M. Artman, and B. Rudy Modulation of Kv4 channels, key components of rat ventricular transient outward K+ current, by PKC Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1775 - H1786. [Abstract] [Full Text] [PDF]
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A. E. Lacerda, M.-L. Roy, E. W. Lewis, and D. Rampe Interactions of the Nonsedating Antihistamine Loratadine with a Kv1.5-Type Potassium Channel Cloned from Human Heart Mol. Pharmacol., August 1, 1997; 52(2): 314 - 322. [Abstract] [Full Text]
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