[Cellular electrophysiological basis of proarrhythmic and antiarrhythmic effects of ischemia-related lipid metabolites].
Lysophosphatidylcholine, an amphiphilic lipid metabolite, accumulates in the ischemic myocardium and plays a pivotal role in the production of arrhythmias. To clarify its cellular ionic mechanism(s), we investigated the effect of 1-palmitoyl-lysophosphatidylcholine (LPC) on the guinea pig ventricular myocytes, using whole cell- and patch-voltage clamp methods. In whole cell recordings, extracellular application of LPC (20-100 microM) depolarized the resting potential within several minutes and produced automatic action potential discharges from the resting and plateau potentials. Such effects were attributed mostly to the decrease in inward going rectifier K current (Ik1). Single channel recordings in the cell attached mode revealed that this decrease in Ik1 is secondary to the reduction of the single channel conductance and not due to decreased open probability. LPC (5-50 microM) also decreased the excitatory Na+ current (INa) in an all-or-nothing manner, depending upon the concentration used. Such decreases in the resting potential and peak INa could be responsible for the marked retardation of conduction velocity and therefore production of reentry. Another amphiphilic lipid metabolite, a long-chain acylcarnitine or 1-palmitoylcarnitine (PALC), had LPC-like depressant effects on INa, albeit the effect was reversible in the majority of cells tested. On the other hand, a short-chain acylcarnitine, 1-propionylcarnitine (PROC) did not affect the INa by itself even at a high concentration (50-500 microM), whereas it prevented the LPC's depressant effect on INa. Like PROC, the middle-chain acylcarnitine, e.g., 1-hexanoylcarnitine (HEXC) did not decrease the INa, but prevented the LPC's deleterious effects on INa, albeit the latter effect was much weaker than that of PROC.(ABSTRACT TRUNCATED AT 250 WORDS)
Arita
M
M
Department of Physiology, Oita Medical University.
Sato
T
T
Ishida
H
H
Nakazawa
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D002331:Carnitine / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
D008244:Lysophosphatidylcholines; D002331:Carnitine