Linalool suppresses voltage-gated currents in sensory neurons and cerebellar Purkinje cells

Abstract

Linalool is a major component of essential oils and possesses various biological effects in sensory or central nervous systems. To investigate the pharmacological and biophysical effects of linalool on voltage-gated currents in sensory neurons, we used the whole-cell patch clamp and the Ca(2+) imaging techniques. Under the voltage clamp, membrane depolarization generated time- and voltage-dependent current responses in newt olfactory receptor cells (ORCs). Linalool significantly and reversibly suppressed the voltage-gated currents in ORCs. The dose-suppression relation of linalool for the voltage-gated Na(+) current could be fitted by the Hill equation with a half-blocking concentration of 0.56 mM and a Hill coefficient of 1.2. To test whether linalool suppresses voltage-gated currents in ORCs specifically or suppresses currents in other neurons generally, we next examined the effects of linalool on voltage-gated currents in newt retinal neurons and rat cerebellar Purkinje cells. Linalool suppressed the voltage-gated currents not only in retinal horizontal cells and ganglion cells but also in Purkinje cells. Furthermore, bath application of linalool inhibited the KCl-induced [Ca(2+)](i) response of ORCs, suggesting that linalool suppresses Ca(2+) currents in ORCs. These results suggest that linalool non-selectively suppresses the voltage-gated currents in newt sensory neurons and rat cerebellar Purkinje cells.

Chemical structures of odorants that suppress ion channels in the olfactory receptor cell

“…(?60.0 mV at 24°C). The shape of waveforms, the I-V relationship, and the reversal potential were essentially the same as those obtained in previous work on newt ORCs [17].…”

Essential oils components as a new path to understand ion channel molecular pharmacology

“…Elisabetsky et al (1995) described that linalool inhibits glutamatergic neurons and later Sugawara et al (2000) observed that it also affected human brain beta waves amplitude. Earlier studies in newt olfactory receptor cells, newt retinal neurons and rat cerebellar Purkinje cells demonstrated that linalool non-selectively but reversibly suppressed the voltagegated currents (Narusuye et al, 2005). In the same report it was shown that linalool reduced KCl-induced intracellular Ca 2+ elevation without affecting the machinery responsible for intracellular Ca 2+ signaling (Narusuye et al, 2005).…”

Local Anaesthetic Properties vs. Neurotoxicity for (+)- and (−)-Carvone: An Ex Vivo Electrophysiological Study

“…The local anaesthetic effects of carvones, as expressed by the inhibition of CAP, which is partially extinguished by nerve washing, could be a result of blockages of VGNaC, which is considered to be the main target of local anaesthetics [16,17]. The same mechanism has been proposed for the local anaesthetic action of linalool [18]. Yet another mechanism was proposed for the action of (−)-carvone, which was recently identified as a novel agonist of TRPV-1 channels [9], thus being a promising target for the development of analgesic drugs [10,11].…”