title: The mechanotransduction of the crayfish stretch receptor neurone can be differentially activated or inactivated by local anaesthetics.
abstract: The effect of the local anaesthetics lidocaine, its meta-isomer, LL33, bupivacaine, tetracaine and procaine on the transducer properties of the stretch receptor neurone of the crayfish Pacifastacus leniusculus was investigated using a two microelectrode voltage clamp. Lidocaine increased the receptor current whereas LL33, bupivacaine and tetracaine reduced the receptor current in a reversible dose-dependent way. Procaine did not affect the receptor responses. The onset of the effect was generally slow in the order of minutes. Lidocaine increased the conductance of the mechanotransducer 50 +/- 7% (mean +/- SD, n = 4) and changed the reversal potential -8 +/- 1 mV (mean +/- SEM, n = 8), which indicates a major K+ conductance increase through the mechanosensitive channels. The other local anaesthetics increase the K+ conductance of the mechanotransducer without increasing the total conductance, which suggests that only P(Na)/P(K) is changed. These substances seem to have a Ca2+ dependent effect on the gating properties of the mechanosensitive channels in addition to their effect on the permeability through the channels as compared with lidocaine. All local anaesthetics investigated decreased the leak conductance of the receptor neurone. The effects of local anaesthetics on the mechanosensitive channels whether activating or blocking is correlated to the oil:water distribution coefficients and their relative hydrophobicity/hydrophilicity ratio. The results are consistent with the hypothesis that the local anaesthetic effect is mediated by changes in the lipid phase of the membrane.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J H
authors.initials: JH
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Rydqvist
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003400:Astacoidea; D002045:Bupivacaine / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004594:Electrophysiology; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008465:Mechanoreceptors / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D011343:Procaine / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine; D002118:Calcium; D002045:Bupivacaine