Functional expression of a GFP-tagged Kv1.5 α-subunit in mouse ventricle

Huilin Li, Weinong Guo, Haodong Xu, Rebecca Hood, Andrew T. Benedict, Jeanne M. Nerbonne

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The experiments here were undertaken to determine the feasibility of increasing the cell surface expression of voltage-gated ion channels in cardiac cells in vivo and to explore the functional consequences of ectopic channel expression. Transgenic mice expressing a green fluorescent protein (GFP)-tagged, voltage-gated K+ (Kv) channel α-subunit, Kv1.5-GFP, driven by the cardiac-specific α-MHC promoter, were generated. In recent studies, Kv1.5 has been shown to encode the micromolar 4-aminopyridine (4-AP)-sensitive delayed rectifier K+ current (IK, slow) in mouse myocardium. Unexpectedly, Kv1.5-GFP expression is heterogeneous in the ventricles of these animals. Although no electrocardiographic abnormalities were evident, expression of Kv1.5-GFP results in marked decreases in action potential durations in GFP-positive ventricular myocytes. In voltage-clamp recordings from GFP-positive ventricular myocytes, peak outward K+ currents are significantly higher, and their waveforms are distinct from those recorded from wild-type cells. Pharmacological experiments revealed a selective increase in a micromolar 4-AP-sensitive current, similar to the 4-AP-sensitive component of IK,slow in wild-type cells. The inactivation rate of the "overexpressed" current, however, is significantly slower than the Kv1.5-encoded component of IK,slow in wild-type cells, suggesting differences in association with accessory subunits and/or posttranslational processing.

Original languageEnglish
Pages (from-to)H1955-H1967
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number5 50-5
StatePublished - Dec 18 2001

Keywords

  • Transgenic mice
  • Ventricular myocytes

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