Lysophosphatidylcholine augments Cav3.2 but not Cav3.1 T-type Ca2+ channel current expressed in HEK-293 cells

Lysophosphatidylcholine (LPC) has been shown to induce electrophysiological disturbances to arrhythmogenesis. However, the effects of LPC on the low-voltage-activated T-type Ca2+ channels in the heart are not understood yet. We found that LPC increases the T-type Ca2+ channel current (I-Ca.T) in neonatal rat cardiomyocytes. To further investigate the underlying modulatory mechanism of LPC on T-type Ca2+ channels, we utilized HEK-293 cells stably expressing alpha 1G and alpha 1H subunits (HEK-293/alpha 1G and HEK-293/alpha 1H), by use of patch-clamp techniques. A low concentration of LPC (10 mu mol/l) significantly increased Ca(v)3.2 I-Ca.T (alpha 1H) that were similar to those observed in neonatal rat cardiomyocytes. Activation and steady-state inactivation curves were shifted in the hyperpolarized direction by 5.1 +/- 0.2 and 4.6 +/- 0.4 mV, respectively, by application of 10 mu mol/l LPC. The pretreatment of cells with a protein kinase C inhibitor (chelerythrine) attenuated the effects of LPC on I-Ca.T (alpha 1H). However, the application of LPC failed to modify Ca(v)3.1 (alpha 1G) I-Ca.T at concentrations of 10-50 mu mol/l. In conclusion, these data demonstrate that extracellularly applied LPC augments Ca(v)3.2 I-Ca.T (alpha 1H) but not Ca(v)3.1 I-Ca.T (alpha 1G) in a heterologous expression system, possibly by modulating protein kinase C signaling. Copyright (C) 2006 S. Karger AG, Basel.