Electrical remodeling in a canine model of ischemic cardiomyopathy

Xian Sheng Liu, Min Jiang, Mei Zhang, Daniel Tang, Henry F. Clemo, Robert S.D. Higgins, Gea Ny Tseng

Research output: Contribution to journalArticlepeer-review

Abstract

The nature of electrical remodeling in a canine model of ischemic cardiomyopathy (ICM; induced by repetitive intracoronary microembolizations) that exhibits spontaneous ventricular tachycardia is not entirely clear. We used the patch-clamp technique to record action potentials and ionic currents of left ventricular myocytes isolated from the region affected by microembolizations. We also used the immunoblot technique to examine channel subunit expression in adjacent affected tissue. Ventricular myocytes and tissue isolated from the corresponding region of normal hearts served as control. ICM myocytes had prolonged action potential duration (APD) and more pronounced APD dispersion. Slow delayed rectifier current (IKs) was reduced at voltages positive to 0 mV, along with a negative shift in its voltage dependence of activation. Immunoblots showed that there was no change in KCNQ1.1 (I Ks pore-forming or α-subunit), but KCNE1 (IKs auxiliary or β-subunit) was reduced, and KCNQ1.2 (a truncated KCNQ1 splice variant with a dominant-negative effect on IKs) was increased. Transient outward current (Ito) was reduced, along with an acceleration of the slow phase of recovery from inactivation. Immunoblots showed that there was no change in Kv4.3 (α-subunit of fast-recovering I to component), but KChIP2 (β-subunit of fast-recovering component) and Kv1.4 (α-subunit of slow-recovering component) were reduced. Inward rectifier current was reduced. L-type Ca current was unaltered. The immunoblot data provide mechanistic insights into the observed changes in current amplitude and gating kinetics of IKs and Ito. We suggest that these changes, along with the decrease in inward rectifier current, contribute to APD prolongation in ICM hearts.

Original languageEnglish (US)
Pages (from-to)H560-H571
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Keywords

  • Arrhythmia
  • Heart failure
  • Oocyte expression
  • Voltage clamp

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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