Farnesol blocks the L-type Ca2+ channel by targeting the α(1C) subunit

Ulrich C. Luft, Rostislav Bychkov, Maik Gollasch, Volkmar Gross, Jean Baptiste Roullet, David A. McCarron, Christian Ried, Franz Hofmann, Yoram Yagil, Chana Yagil, Hermann Haller, Friedrich C. Luft

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34 Scopus citations


We recently demonstrated that farnesol, a 15-carbon isoprenoid, blocks L-type Ca2+ channels in vascular smooth muscle cells. To elucidate farnesol's mechanism of action, we performed whole-cell and perforated-patch clamp experiments in rat aortic A7r5 cells and in Chinese hamster ovary (CHO) C9 cells expressing smooth muscle Ca2+ channel α(1c) subunits. Farnesol dose-dependently and voltage-independently inhibited Ba2+ currents in both A7r5 and CHOC9 cells, with similar half-maximal inhibitions at 2.6 and 4.3 mmol/L, respectively (P=NS). In both cell lines, current inhibition by farnesol was prominent over the whole voltage range without changes in the current-voltage relationship peaks. Neither intracellular infusion of the stable GDP analogue guanosine-5'-O-(2-thiodiphosphate) (100 mmol/L) via the patch pipette nor strong conditioning membrane depolarization prevented the inhibitory effect of farnesol, which indicates G protein-independent inhibition of Ca2+ channels. In an analysis of the steady-state inactivation curve for voltage dependence, farnesol induced a significant, negative shift (≃10 mV) of the potential causing 50% channel inactivation in both cell lines (P<0.001). In contrast, the steepness factor characterizing the voltage sensitivity of the channels was unaffected. Unlike pharmacological Ca2+ channel blockers, farnesol blocked Ca2+ currents in the resting state: initial block was 63±8% in A7r5 cells and 50±9% in CHOC9 cells at a holding potential of -80 mV. We then gave 500 mg/kg body weight farnesol by garage to Sabra hypertensive and normotensive rats and found that farnesol reduced blood pressure significantly in the hypertensive strain for at least 48 hours. We conclude that farnesol may represent an endogenous smooth muscle L-type Ca2+ channel antagonist. Because farnesol is active in cells expressing only the pore-forming α1 subunit, the data further suggest that this subunit represents the molecular target for farnesol binding and principal action. Finally, farnesol has a blood pressure-lowering action that may be relevant in vivo.

Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number4
StatePublished - 1 Jan 1999


  • Calcium channel blockers
  • Farnesol
  • L- class channels
  • Patch clamp
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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