Modulation of cardiac sodium channel gating by lysophosphatidylcholine

The effects of lysophosphatidylcholine (LPC) on Na channels have been investigated in inside-out patches of adult rat ventricular cells using the patch-clamp technique. Applying LPC (9-25 μm) to the inner side of the membrane reduced peak Na current (I_Na) and prolonged the time course of I_Na inactivation. Both effects increased with duration of LPC exposure. Analysis of single-channel behavior revealed that after 15-20 min of exposure to LPC, Na channels displayed 2 types of gating behavior. One type consisted of normal kinetics and the other consisted of long-lasting burst (LB) of Na channel openings (up to the 300 ms bursts of the test pulse). This modification in gating resulted in the initial appearance of a slowly decaying and later a noninactivating component of I_Na in the ensemble average current. The slope conductance and reversal potential of these modified channels remained unchanged from control. Overall open time distribution for long bursting kinetics channels was biexponential, indicating existence of two long-lasting bursting modes, one with fast kinetics (LB-f, mean open time 1.2 ms) and one with slow kinetics (LB-s, mean open time 13.7 ms). These data indicate that exposure to LPC results in the slow interconversion of Na channels between several modes of activity, including those in which inactivation occurs slowly or not at all.