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Enhanced functional expression of transient outward current in hypertrophied feline myocytes

Summary

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch voltage-clamp studies designed to explain these changes in the action potential suggest that the only component of the membrane current recorded from feline right ventricular (RV) myocytes found to be substantially different from normal is the 4-aminopyridine-sensitive transient outward current (Ito). However, it was not clear if the change in Ito could explain the changes in the action potential of hypertrophied cardiocytes, nor was it clear if these changes reflect an alteration in the electrophysiological character of the channels underlying Ito. A kinetic comparison of Ito elicited by hypertrophied RV myocytes with that elicited by comparable normal RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak Ito recorded from hypertrophied myocytes arises because the current density increases and not because of any alteration in the kinetic parameters governing the current. This finding suggests that in hypertrophy additional normal channels are expressed rather than a kinetically different channel subtype emerging. Investigations designed to determine if enhancement of Ito could explain the hypertrophy-induced changes in plateau voltage and action potential duration suggest that a change in Ito density can indeed explain the entire effect of hypertrophy on RV action potentials. If this notion is correct, the likelihood of “sudden death” in patients with myocardial hypertrophy might be decreased by a blocker selective for cardiac Ito.

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Correspondence to Dr. Robert E. Ten Eick.

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Ten Eick, R.E., Zhang, K., Harvey, R.D. et al. Enhanced functional expression of transient outward current in hypertrophied feline myocytes. Cardiovasc Drug Ther 7, 611–619 (1993). https://doi.org/10.1007/BF00877628

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Key Words

  • transient outward current
  • cardiac hypertrophy
  • whole-cell voltage clamp
  • cardiac myocytes
  • right ventricular hypertrophy
  • Ito regulation