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Farnesol blocks the L-type Ca2+ channel by targeting the alpha 1C subunit
U C Luft1, R Bychkov, M Gollasch
1Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Virchow Klinikum-Charité, Humboldt University of Berlin, Berlin, Germany. luft@fvk-berlin.de
Arteriosclerosis, Thrombosis, and Vascular Biology
|April 9, 1999
Summary
Farnesol, an isoprenoid, inhibits L-type calcium channels in vascular smooth muscle cells. This compound lowers blood pressure in hypertensive rats, suggesting it acts as an endogenous calcium channel antagonist.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Molecular Biology
Background:
- Farnesol, a 15-carbon isoprenoid, has been shown to block L-type Ca2+ channels in vascular smooth muscle cells.
- Understanding the mechanism of farnesol's action on these channels is crucial for its potential therapeutic applications.
Purpose of the Study:
- To elucidate the mechanism of action of farnesol on L-type Ca2+ channels.
- To investigate whether farnesol acts as a G protein-dependent or independent inhibitor.
- To determine the effect of farnesol on blood pressure in vivo.
Main Methods:
- Whole-cell and perforated-patch clamp electrophysiology in rat aortic A7r5 and CHO C9 cells expressing Ca2+ channel alpha 1C subunits.
- G-protein inhibition assays using guanosine-5'-O-(2-thiodiphosphate).
- In vivo administration of farnesol to hypertensive and normotensive rats.
Main Results:
- Farnesol inhibited Ba2+ currents in a dose-dependent and voltage-independent manner in both cell lines.
- The inhibition was G protein-independent and shifted the steady-state inactivation curve negatively.
- Farnesol significantly reduced blood pressure in hypertensive rats for at least 48 hours.
Conclusions:
- Farnesol acts as a G protein-independent antagonist of smooth muscle L-type Ca2+ channels.
- The pore-forming alpha1 subunit is likely the molecular target for farnesol.
- Farnesol exhibits a blood pressure-lowering effect in vivo, suggesting therapeutic potential.
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