Effects of lysophosphatidylcholine on resting potassium conductance of isolated guinea pig ventricular cells.
We studied the effects of lysophosphatidylcholine (LPC), a toxic metabolite of ischemia, on the inward rectifier potassium channel current in isolated guinea pig ventricular cells. LPC (10-50 microM) added to the external solution decreased the resting membrane potential and occasionally induced repetitive action potential discharges, with or without loss of repolarization. In voltage clamp studies, LPC (20 microM) decreased the conductance at the levels of resting potentials (approximately equal to -80 mV) from 26 +/- 8 nS to 16 +/- 3 nS (mean and SD, n = 4) within 10 min. Prolonged application of LPC (greater than 12 min) produced transient inward currents after depolarizing clamp pulses, thereby suggesting that the LPC elevated intracellular Ca2+ concentrations. The effect of LPC on the single inward rectifier K channel current was examined using the patch clamp technique in a cell-attached mode. LPC decreased the single channel conductance, depending on the concentration (5-100 microM). The slope conductance in the presence of 150 mM K+ in the pipette decreased from 45 +/- 7 pS (control) to 32 +/- 17, 20 +/- 19, and 14 +/- 10 pS for 5, 20 and 100 microM LPC, respectively. LPC induced little change with regard to probability of the channel opening. These results suggest that LPC depolarizes membrane by decreasing single channel conductance of the inward rectifier K channel. This reduction partially contributes to the alleged LPC-induced abnormal automaticities and conduction disturbances in the heart.
Kiyosue
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Arita
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D000818:Animals; D002478:Cells, Cultured; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology*; D007473:Ion Channels / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010783:Photometry; D011188:Potassium / Q000032:analysis / Q000378:metabolism*
D007473:Ion Channels; D008244:Lysophosphatidylcholines; D011188:Potassium