Role of heteromultimers in the generation of myocardial transient outward K+ currents

Weinong Guo, Huilin Li, Franck Aimond, David C. Johns, Kenneth J. Rhodes, James Trimmer, Jeanne M. Nerbonne

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Previous studies have demonstrated a role for Kv4 α subunits in the generation of the fast transient outward K+ current, Ito,f, in the mammalian myocardium. The experiments here were undertaken to explore the role of homomeric/heteromeric assembly of Kv4.2 and Kv4.3 and of the Kv channel accessory subunit, KChIP2, in the generation of mouse ventricular Ito,f. Western blots reveal that the expression of Kv4.2 parallels the regional heterogeneity in Ito,f density, whereas Kv4.3 and KChIP2 are uniformly expressed in adult mouse ventricles. Antisense oligodeoxynucleotides (AsODNs) targeted against Kv4.2 or Kv4.3 selectively attenuate Ito,f in mouse ventricular cells. Adenoviral-mediated coexpression of Kv4.2 and Kv4.3 in HEK-293 cells and in mouse ventricular myocytes produces transient outward K+ currents with properties distinct from those produced on expression of Kv4.2 or Kv4.3 alone, and the gating properties of the heteromeric Kv4.2/Kv4.3 channels in ventricular cells are more similar to native Ito,f than are the homomeric Kv4.2 or Kv4.3 channels. Biochemical studies reveal that Kv4.2, Kv4.3, and KChIP2 coimmunoprecipitate from adult mouse ventricles. In addition, most of the Kv4.2 and KChIP2 are associated with Kv4.3 in situ. Taken together, these results demonstrate that functional mouse ventricular Ito,f channels are heteromeric, comprising Kv4.2/Kv4.3 α subunits and KChIP2. The results here also suggest that Kv4.2 is the primary determinant of the regional heterogeneity in Ito,f expression in adult mouse ventricle.

Original languageEnglish (US)
Pages (from-to)586-593
Number of pages8
JournalCirculation Research
Volume90
Issue number5
DOIs
StatePublished - Mar 22 2002
Externally publishedYes

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Oligodeoxyribonucleotides
HEK293 Cells
Muscle Cells
Myocardium
Western Blotting

Keywords

  • Adenoviral gene transfer
  • I
  • KChIP2
  • Kv4 α subunits

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Guo, W., Li, H., Aimond, F., Johns, D. C., Rhodes, K. J., Trimmer, J., & Nerbonne, J. M. (2002). Role of heteromultimers in the generation of myocardial transient outward K+ currents. Circulation Research, 90(5), 586-593. https://doi.org/10.1161/01.RES.0000012664.05949.E0

Role of heteromultimers in the generation of myocardial transient outward K+ currents. / Guo, Weinong; Li, Huilin; Aimond, Franck; Johns, David C.; Rhodes, Kenneth J.; Trimmer, James; Nerbonne, Jeanne M.

In: Circulation Research, Vol. 90, No. 5, 22.03.2002, p. 586-593.

Research output: Contribution to journalArticle

Guo, W, Li, H, Aimond, F, Johns, DC, Rhodes, KJ, Trimmer, J & Nerbonne, JM 2002, 'Role of heteromultimers in the generation of myocardial transient outward K+ currents', Circulation Research, vol. 90, no. 5, pp. 586-593. https://doi.org/10.1161/01.RES.0000012664.05949.E0
Guo, Weinong ; Li, Huilin ; Aimond, Franck ; Johns, David C. ; Rhodes, Kenneth J. ; Trimmer, James ; Nerbonne, Jeanne M. / Role of heteromultimers in the generation of myocardial transient outward K+ currents. In: Circulation Research. 2002 ; Vol. 90, No. 5. pp. 586-593.
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