Abstract
Lysophosphatidylcholine (LPC) has been shown to induce electrophysiological disturbances to arrhythmogenesis. However, the effects of LPC on the low-voltage-activated T-type Ca<sup>2+</sup> channels in the heart are not understood yet. We found that LPC increases the T-type Ca<sup>2+</sup> channel current (I<sub>Ca.T</sub>) in neonatal rat cardiomyocytes. To further investigate the underlying modulatory mechanism of LPC on T-type Ca<sup>2+</sup> channels, we utilized HEK-293 cells stably expressing α1G and α1H subunits (HEK-293/α1G and HEK-293/α1H), by use of patch-clamp techniques. A low concentration of LPC (10 µmol/l) significantly increased Ca<sub>v</sub>3.2 I<sub>Ca.T</sub> (α1H) 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 µmol/l LPC. The pretreatment of cells with a protein kinase C inhibitor (chelerythrine) attenuated the effects of LPC on I<sub>Ca.T</sub> (α1H). However, the application of LPC failed to modify Ca<sub>v</sub>3.1 (α1G) I<sub>Ca.T</sub> at concentrations of 10–50 µmol/l. In conclusion, these data demonstrate that extracellularly applied LPC augments Ca<sub>v</sub>3.2 I<sub>Ca.T</sub> (α1H) but not Ca<sub>v</sub>3.1 I<sub>Ca.T</sub> (α1G) in a heterologous expression system, possibly by modulating protein kinase C signaling.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.