© 1996 American Heart Association, Inc.
Articles |
Developmental Changes in Ionic Channel Activity in the Embryonic Murine Heart
From the Department of Physiology, University of Rochester (NY) School of Medicine and Dentistry (M.P.D., R.H.A., R.S.K.), and the Department of Medicine, School of Medicine, University of California, San Diego (P.D., S.K., K.R.C.).
Correspondence to R.S. Kass, PhD, Department of Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642. E-mail rsks@uhura.cc.rochester.edu.
Abstract We have isolated murine embryonic atrial and ventricular cells derived from timed-pregnant females at different periods and used patch-clamp procedures to investigate age- and chamber-specific expression of ionic channels in the developing fetal mouse. Our data indicate that L-type Ca2+ channels play a dominant role in excitation during early murine cardiac embryogenesis and that Na+ channel expression increases dramatically just before birth. K+ channel expression is particularly sensitive to changes during development. Neither atrial nor ventricular cells express a slowly activating component of delayed rectification (IKs) until just before birth, and inwardly rectifying channel activity, associated with determination of cellular resting potential, is not markedly apparent until late stages of embryogenesis. Instead, we find robust expression of the ATP-regulated K+ channel at early and late stages of embryonic development, which may indicate a novel functional role for this channel during morphogenesis of the heart. These results have important implications for the physiology and development of the murine cardiac conduction system and will also serve as a baseline for future studies designed to investigate developmental changes of ion channel expression in the myocardium of both wild-type and genetically modified mice.
Key Words: ion channels • heart • development • mouse
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|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 O Gryshchenko, I. Fischer, M Dittrich, S Viatchenko-Karpinski, J Soest, M. Bohm-Pinger, P Igelmund, B. Fleischmann, and J Hescheler Role of ATP-dependent K(+) channels in the electrical excitability of early embryonic stem cell-derived cardiomyocytes J. Cell Sci., January 9, 1999; 112(17): 2903 - 2912. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Kolossov, B.K. Fleischmann, Q. Liu, W. Bloch, S. Viatchenko-Karpinski, O. Manzke, G.J. Ji, H. Bohlen, K. Addicks, and J. Hescheler Functional Characteristics of ES Cell-derived Cardiac Precursor Cells Identified by Tissue-specific Expression of the Green Fluorescent Protein J. Cell Biol., December 28, 1998; 143(7): 2045 - 2056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 P. Gruber, S. Kubalak, and K. Chien Downregulation of atrial markers during cardiac chamber morphogenesis is irreversible in murine embryos Development, January 11, 1998; 125(22): 4427 - 4438. [Abstract] [PDF]
|
|
|
|
|
|
B. B. Keller, M. Yoshigi, and J. P. Tinney Ventricular-vascular uncoupling by acute conotruncal occlusion in the stage 21 chick embryo Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2861 - H2866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
L. Wang and H. J. Duff Developmental Changes in Transient Outward Current in Mouse Ventricle Circ. Res., July 19, 1997; 81(1): 120 - 127. [Abstract] [Full Text]
|
|
|
|
|
|
W. Guo, K. Kamiya, and J. Toyama Differential effects of chronic membrane depolarization on the K+ channel activities in cultured rat ventricular cells Cardiovasc Res, January 1, 1997; 33(1): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, Z.-P. Feng, C. S. Kondo, R. S. Sheldon, and H. J. Duff Developmental Changes in the Delayed Rectifier K+ Channels in Mouse Heart Circ. Res., July 1, 1996; 79(1): 79 - 85. [Abstract] [Full Text]
|
|
|
|
|
|
C. Seisenberger, V. Specht, A. Welling, J. Platzer, A. Pfeifer, S. Kuhbandner, J. Striessnig, N. Klugbauer, R. Feil, and F. Hofmann Functional Embryonic Cardiomyocytes after Disruption of the L-type alpha 1C (Cav1.2) Calcium Channel Gene in the Mouse J. Biol. Chem., December 8, 2000; 275(50): 39193 - 39199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Vaidya, H. S. Tamaddon, C. W. Lo, S. M. Taffet, M. Delmar, G. E. Morley, and J. Jalife Null Mutation of Connexin43 Causes Slow Propagation of Ventricular Activation in the Late Stages of Mouse Embryonic Development Circ. Res., June 8, 2001; 88(11): 1196 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M.B. Anumonwo, Y. N. Tallini, F. J. Vetter, and J. Jalife Action Potential Characteristics and Arrhythmogenic Properties of the Cardiac Conduction System of the Murine Heart Circ. Res., August 17, 2001; 89(4): 329 - 335. [Abstract] [Full Text] [PDF]
|
|