Differential mechanism of block of palmitoyl lysophosphatidylcholine and of palmitoylcarnitine on inward rectifier K+ channels of guinea-pig ventricular myocytes.
We investigated the effect of lysophosphatidylcholine (lysoPtdCho) and palmitoylcarnitine (PamCar), ischemia-induced amphipathic lipid metabolites, on the inward rectifier K+ channel in guinea-pig ventricular cells, under whole-cell and cell-attached configurations with patch-clamp techniques. (a) Both lysoPtdCho (10-50 microM) and PamCar (10-50 microM) depolarized the resting membrane potential (RP), retarded the repolarization of action potential, provoked spontaneous action potential discharges from oscillatory afterpotentials, and eventually caused a sudden rise of the RP to plateau levels. (b) These lysoPtdCho- or PamCar-induced depolarizations of RP were due to a decrease in the inward rectifier K+ current (IK1), and the sudden rise of the RP could be accounted for by a crossover of N-shaped current-voltage relationship on the voltage axis (zero current line) more than once. (c) Single-channel studies in the cell-attached mode revealed that lysoPtdCho (5-100 microM) decreased the conductance of the single IK1 channel with little change in its open probability, whereas PamCar (10-50 microM) did so by decreasing the open probability, with the channel conductance unaltered. (d) A short-chain acylcarnitine, l-propionylcarnitine (PpCar, 100 microM), prevented the depressant effect of lysoPtdCho (50 microM), but not of PamCar (50 microM), on the IK1. (e) Both lysoPtdCho and PamCar produced identical electrophysiological alterations on the membrane potential and IK1 in whole-cell recordings. However, molecular mechanisms involved in the effects of these toxic metabolites on single IK1 channels differ.
Sato
T
T
Department of Physiology, Oita Medical University, Japan.
Arita
M
M
Kiyosue
T
T
D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010477:Perfusion; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects
D008244:Lysophosphatidylcholines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C006065:We 201; D010172:Palmitoylcarnitine