Effects of Lysophosphoglycerides on KATP Channels in Cardiac Ventricular Cells: Blockage or Rundown?

The effects of lysophosphatidylcholine (LPC), an ischemia-derived amphipathic lysophosphoglyceride, on ATP-sensitive K+ (KATP) channels of guinea pig ventricular cells were examined using the patch-clamp technique in inside-out or cell-attached patch configuration. KATP channel activity of the inside-out patch declined gradually with time after patch excision in the ATP-free bath solution (rundown). Under control conditions, more than 10min was required for the KATP channel activity to decrease to less than 10% of the initial activity. Application of LPC (10–50μM) from the intracellular side of the membrane irreversibly depressed the channel activity to less than 10% within 4 min. LPC (10μM) applied from the intracellular side of the membrane did not affect the trypsin-treated KATP channel current (lmg/ml for 2min), which never went into rundown. After channel rundown, continued application of uridine diphosphate (UDP, 3mM) led to reactivation of the KATP channel. LPC (10 μM) did not affect UDP-induced KATP channel activity. In the cell-attached mode, LPC (50μM) applied from outside the membrane (i. e., LPC in the pipette) had no effect on the KATP channel current that had been activated by application of carbonyl cyanide p-(trifluoro-methoxy) phenylhydrazone (FCCP) (0.1μM), a metabolic inhibitor. These results suggested that LPC does not block the KATP channel but merely facilitates the rundown of this channel when applied from the intracellular side of the membrane; LPC had no effect on the KATP channels when applied from the extracellular side of the membrane.