Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1997 Nov 1;504(Pt 3):557–563. doi: 10.1111/j.1469-7793.1997.557bd.x

A rapidly activating sustained K+ current modulates repolarization and excitation-contraction coupling in adult mouse ventricle.

C Fiset 1, R B Clark 1, T S Larsen 1, W R Giles 1
PMCID: PMC1159960  PMID: 9401964

Abstract

1. The K+ currents which control repolarization in adult mouse ventricle, and the effects of changes in action potential duration on excitation-contraction coupling in this tissue, have been studied with electrophysiological methods using single cell preparations and by recording mechanical parameters from an in vitro working heart preparation. 2. Under conditions where Ca(2+)-dependent currents were eliminated by buffering intracellular Ca2+ with EGTA, depolarizing voltage steps elicited two rapidly activating outward K+ currents: (i) a transient outward current, and (ii) a slowly inactivating or 'sustained' delayed rectifier. 3. These two currents were separated pharmacologically by the K+ channel blocker 4-amino-pyridine (4-AP). 4-AP at concentrations between 3 and 200 microM resulted in (i) a marked increase in action potential duration and a large decrease in the sustained K+ current at plateau potentials, as well as (ii) a significant increase in left ventricular systolic pressure in the working heart preparation. 4. The current-voltage (I-V) relation, kinetics, and block by low concentrations of 4-AP strongly suggest that the rapid delayed rectifier in adult mouse ventricles is the same K+ current (Kv1.5) that has been characterized in detail in human and canine atria. 5. These results show that the 4-AP-sensitive rapid delayed rectifier is a very important repolarizing current in mouse ventricle. The enhanced contractility produced by 4-AP (50 microM) in the working heart preparation demonstrates that modulation of the action potential duration, by blocking a K+ current, is a very significant inotropic variable.

Full text

PDF
557

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Attali B., Lesage F., Ziliani P., Guillemare E., Honoré E., Waldmann R., Hugnot J. P., Mattéi M. G., Lazdunski M., Barhanin J. Multiple mRNA isoforms encoding the mouse cardiac Kv1-5 delayed rectifier K+ channel. J Biol Chem. 1993 Nov 15;268(32):24283–24289. [PubMed] [Google Scholar]
  2. Becker K. D., Gottshall K. R., Chien K. R. Strategies for studying cardiovascular phenotypes in genetically manipulated mice. Hypertension. 1996 Mar;27(3 Pt 2):495–501. doi: 10.1161/01.hyp.27.3.495. [DOI] [PubMed] [Google Scholar]
  3. Benndorf K., Nilius B. Properties of an early outward current in single cells of the mouse ventricle. Gen Physiol Biophys. 1988 Oct;7(5):449–466. [PubMed] [Google Scholar]
  4. Bouchard R., Fedida D. Closed- and open-state binding of 4-aminopyridine to the cloned human potassium channel Kv1.5. J Pharmacol Exp Ther. 1995 Nov;275(2):864–876. [PubMed] [Google Scholar]
  5. Brooks W. W., Apstein C. S. Effect of treppe on isovolumic function in the isolated blood-perfused mouse heart. J Mol Cell Cardiol. 1996 Aug;28(8):1817–1822. doi: 10.1006/jmcc.1996.0171. [DOI] [PubMed] [Google Scholar]
  6. Christensen G., Wang Y., Chien K. R. Physiological assessment of complex cardiac phenotypes in genetically engineered mice. Am J Physiol. 1997 Jun;272(6 Pt 2):H2513–H2524. doi: 10.1152/ajpheart.1997.272.6.H2513. [DOI] [PubMed] [Google Scholar]
  7. Clark R. B., Bouchard R. A., Giles W. R. Action potential duration modulates calcium influx, Na(+)-Ca2+ exchange, and intracellular calcium release in rat ventricular myocytes. Ann N Y Acad Sci. 1996 Apr 15;779:417–429. doi: 10.1111/j.1749-6632.1996.tb44817.x. [DOI] [PubMed] [Google Scholar]
  8. Davies M. P., An R. H., Doevendans P., Kubalak S., Chien K. R., Kass R. S. Developmental changes in ionic channel activity in the embryonic murine heart. Circ Res. 1996 Jan;78(1):15–25. doi: 10.1161/01.res.78.1.15. [DOI] [PubMed] [Google Scholar]
  9. Feng J., Wible B., Li G. R., Wang Z., Nattel S. Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ Res. 1997 Apr;80(4):572–579. doi: 10.1161/01.res.80.4.572. [DOI] [PubMed] [Google Scholar]
  10. Grissmer S., Nguyen A. N., Aiyar J., Hanson D. C., Mather R. J., Gutman G. A., Karmilowicz M. J., Auperin D. D., Chandy K. G. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227–1234. [PubMed] [Google Scholar]
  11. Grupp I. L., Subramaniam A., Hewett T. E., Robbins J., Grupp G. Comparison of normal, hypodynamic, and hyperdynamic mouse hearts using isolated work-performing heart preparations. Am J Physiol. 1993 Oct;265(4 Pt 2):H1401–H1410. doi: 10.1152/ajpheart.1993.265.4.H1401. [DOI] [PubMed] [Google Scholar]
  12. Guo W., Kamiya K., Liu W., Toyama J. Developmental changes of the ultrarapid delayed rectifier K+ current in rat ventricular myocytes. Pflugers Arch. 1997 Feb;433(4):442–445. doi: 10.1007/s004240050298. [DOI] [PubMed] [Google Scholar]
  13. Isenberg G., Klockner U. Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium". Pflugers Arch. 1982 Oct;395(1):6–18. doi: 10.1007/BF00584963. [DOI] [PubMed] [Google Scholar]
  14. Milano C. A., Allen L. F., Rockman H. A., Dolber P. C., McMinn T. R., Chien K. R., Johnson T. D., Bond R. A., Lefkowitz R. J. Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. Science. 1994 Apr 22;264(5158):582–586. doi: 10.1126/science.8160017. [DOI] [PubMed] [Google Scholar]
  15. Nuss H. B., Marban E. Electrophysiological properties of neonatal mouse cardiac myocytes in primary culture. J Physiol. 1994 Sep 1;479(Pt 2):265–279. doi: 10.1113/jphysiol.1994.sp020294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Snyders D. J., Tamkun M. M., Bennett P. B. A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J Gen Physiol. 1993 Apr;101(4):513–543. doi: 10.1085/jgp.101.4.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tamkun M. M., Knoth K. M., Walbridge J. A., Kroemer H., Roden D. M., Glover D. M. Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J. 1991 Mar 1;5(3):331–337. doi: 10.1096/fasebj.5.3.2001794. [DOI] [PubMed] [Google Scholar]
  18. Wang L., Duff H. J. Developmental changes in transient outward current in mouse ventricle. Circ Res. 1997 Jul;81(1):120–127. doi: 10.1161/01.res.81.1.120. [DOI] [PubMed] [Google Scholar]
  19. Wang L., Duff H. J. Identification and characteristics of delayed rectifier K+ current in fetal mouse ventricular myocytes. Am J Physiol. 1996 Jun;270(6 Pt 2):H2088–H2093. doi: 10.1152/ajpheart.1996.270.6.H2088. [DOI] [PubMed] [Google Scholar]
  20. Wang Z., Fermini B., Nattel S. Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ Res. 1993 Dec;73(6):1061–1076. doi: 10.1161/01.res.73.6.1061. [DOI] [PubMed] [Google Scholar]
  21. Yue L., Feng J., Li G. R., Nattel S. Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization. J Physiol. 1996 Nov 1;496(Pt 3):647–662. doi: 10.1113/jphysiol.1996.sp021716. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES