Diminished transient outward currents in rat hypertrophied ventricular myocytes

Fumishi Tomita, Arthur L. Bassett, Robert J. Myerburg, Shinichi Kimura

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Action potential duration is prolonged in ventricular hypertrophy induced by sustained pressure overload. Since the transient outward current (I(to)) is a major factor for determining action potential duration in rat ventricular cells, we used patch-clamp techniques to compare the characteristics of I(to) in normal and hypertrophied left ventricular cells of the rat. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4 to 6 weeks before study. Age-matched normal rats served as controls. Pressure overload increased the heart weight- to-body weight ratio by 47.7%. I(to) was significantly smaller in hypertrophied cells than in normal cells (20.0±1.3 versus 31.0±2.1 pA/pF, respectively, at a test potential of +60 mV; P<.001). There were no differences in the steady-state inactivation, the inactivation time course, and the time course of recovery from inactivation between normal and hypertrophied cells. At the single-channel level, there were no differences in the unitary current amplitude of the single I(to) channel between normal and hypertrophied cells, and the slope conductance was 13.7 picosiemens in normal cells and 13.4 picosiemens in hypertrophied cells. The maximum open- state probability, which was estimated from the ratio of the peak of the ensemble-averaged currents to the single-channel current amplitude, was similar for normal and hypertrophied cells (0.66±0.03 and 0.69±0.04, respectively, at a test potential of +40 mV; P=NS). We conclude that diminished I(to) contributes to action potential prolongation in hypertrophied ventricular cells from pressure-overloaded rat hearts. Reduced I(to) channel density may be responsible for the diminished whole-cell I(to).

Original languageEnglish (US)
Pages (from-to)296-303
Number of pages8
JournalCirculation research
Volume75
Issue number2
DOIs
StatePublished - Aug 1994
Externally publishedYes

Keywords

  • patch clamp
  • pressure overload
  • single channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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