Lysophosphatidylcholine augments Ca(v)3.2 but not Ca(v)3.1 T-type Ca(2+) 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 Ca(2+) channels in the heart are not understood yet. We found that LPC increases the T-type Ca(2+) channel current (I(Ca.T)) in neonatal rat cardiomyocytes. To further investigate the underlying modulatory mechanism of LPC on T-type Ca(2+) channels, we utilized HEK-293 cells stably expressing alpha1G and alpha1H subunits (HEK-293/alpha1G and HEK-293/alpha1H), by use of patch-clamp techniques. A low concentration of LPC (10 micromol/l) significantly increased Ca(v)3.2 I(Ca.T) (alpha1H) 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 micromol/l LPC. The pretreatment of cells with a protein kinase C inhibitor (chelerythrine) attenuated the effects of LPC on I(Ca.T) (alpha1H). However, the application of LPC failed to modify Ca(v)3.1 (alpha1G) I(Ca.T) at concentrations of 10-50 micromol/l. In conclusion, these data demonstrate that extracellularly applied LPC augments Ca(v)3.2 I(Ca.T) (alpha1H) but not Ca(v)3.1 I(Ca.T) (alpha1G) in a heterologous expression system, possibly by modulating protein kinase C signaling.
Department of Cardiovascular Science, Oita University, Oita, Japan.
Mingqi
M
Zheng
Tomoko
T
Uchino
Toshihiko
T
Kaku
Lin
L
Kang
Yan
Y
Wang
Satoshi
S
Takebayashi
Katsushige
K
Ono
D000470:Alkaloids; D000818:Animals; D000831:Animals, Newborn; D053119:Benzophenanthridines; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D000470:Alkaloids; D053119:Benzophenanthridines; C500994:Cacna1g protein, rat; C509958:Cacna1h protein, rat; D020747:Calcium Channels, T-Type; D008244:Lysophosphatidylcholines; D010617:Phenanthridines; C016299:chelerythrine; D011493:Protein Kinase C