Mechanisms for depolarization by l-palmitoylcarnitine in single guinea pig ventricular myocytes

J Cardiovasc Electrophysiol. 1997 Feb;8(2):172-83. doi: 10.1111/j.1540-8167.1997.tb00779.x.

Abstract

Introduction: The changes of the resting potential (RP) and of the current-voltage (I-V) relationship induced by l-palmitoylcarnitine (l-PC) in the presence of the IKI blocker, cesium, or in the presence of the INa/K blocker, ouabain, were tested in guinea pig ventricular myocytes to ascertain the relative contributions of IKI and INa/K suppression to the membrane depolarization caused by this amphiphile.

Methods and results: Ramp voltages were applied to myocytes with the whole cell, patch clamp technique. l-PC (10 microM) produced additional membrane depolarization in the presence of either 10 mM Cs+ or 30 microM ouabain. In the presence of Cs+, l-PC, like 3 microM ouabain, shifted current inward at potentials negative to -20 mV as a result of INa/K blockade. In the presence of 30 microM ouabain, l-PC, like Cs+, shifted current inward at potentials between -27 and -88 mV and outward at potentials negative to -88 mV. This is attributed to IKI block because the current was inwardly rectifying, with a reversal potential near EK. When l-PC or ouabain inhibited INa/K, the presence of an Ni(2+)-sensitive component attributed to INa/Ca distorted the membrane I-V relationship, particularly in the presence of Cs+. The relative contributions of IKI and INa/K block by l-PC were voltage dependent. At the RP, l-PC produced a greater block of INa/K than of IKI.

Conclusion: l-PC depolarizes the resting membrane by inhibiting both IKI and INa/K. It is concluded that suppression of INa/K by l-PC predominates over block of IKI to depolarize the membrane at the RP.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cesium / pharmacology
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Guinea Pigs
  • Heart / drug effects*
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Myocardium / cytology*
  • Nickel / pharmacology
  • Ouabain / pharmacology
  • Palmitoylcarnitine / pharmacology*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Enzyme Inhibitors
  • Potassium Channels
  • Palmitoylcarnitine
  • Cesium
  • Ouabain
  • Nickel
  • Sodium-Potassium-Exchanging ATPase