Regional upregulation of kv2.1-encoded current, IKslow2, in Kv1DN mice is abolished by crossbreeding with Kv2DN mice

Jun Zhou, Sodikdjon Kodirov, Mitsunobu Murata, Peter D. Buckett, Jeanne M. Nerbonne, Gideon Koren

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Overexpression of a truncated Kv1.1 channel transgene in the heart (KvlDN) resulted in mice with a prolonged action potential duration due to marked attenuation of a rapidly activating, slowly inactivating potassium current (IK,slow1) in ventricular myocytes. Optical mapping and programmed electrical stimulation revealed inducible ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Here we show that a delayed rectifier with slower inactivation kinetics (IK,slow2) was selectively upregulated in KvlDN cardiocytes. This electrical remodeling was spatially restricted to myocytes derived from the apex of the left ventricle. Biophysical and pharmacological studies of IK,slow2 indicate that it resembles Kv2-encoded currents. Northern blot analyses and real-time PCR revealed upregulation of Kv2.1 transcript in KvlDN mice. Crossbreeding of KvlDN mice with mice expressing a truncated Kv2.1 polypeptide (Kv2DN) eliminated IK,slow2. In summary, our data indicate that the spatially restrictive upregulation of Kv2.1-encoded currents underlies the increased dispersion of the repolarization observed in KvlDN mice.

Original languageEnglish
Pages (from-to)H491-H500
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number2 53-2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Cardiac arrhythmia
  • Electrophysiology8potassium channels
  • Long QT syndrome

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