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Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine.
- Source :
-
Anesthesiology [Anesthesiology] 2004 Aug; Vol. 101 (2), pp. 430-8. - Publication Year :
- 2004
-
Abstract
- Background: Inhibition of KCNQ2/Q3 channels may cause convulsion in humans. The interaction of bupivacaine with these channels is unknown. The anticonvulsant retigabine activates KCNQ2/Q3 channels and may reverse inhibitory actions of bupivacaine. Potassium channel stimulation may thus constitute a novel approach to treat local anesthetic-induced seizures. The aim of this study was to characterize bupivacaine effects on KCNQ2/Q3 channels and to investigate whether retigabine reverses the effects of the local anesthetic.<br />Methods: KCNQ2/Q3 channels were transiently expressed in Chinese hamster ovary cells. The effects of bupivacaine and retigabine were studied with the patch-clamp technique.<br />Results: Bupivacaine inhibited KCNQ2/Q3 channels in a concentration-dependent and reversible manner. The concentration-response curve was described by a Hill equation (IC50 = 173 +/- 7 microm, Hill coefficient = 1.4 +/- 0.1, mean +/- SEM, n = 37). The inhibitory effect did not differ between bupivacaine and levobupivacaine (42 +/- 4%, n = 7, versus 42 +/- 5%, n = 10; P > 0.05). Ropivacaine was four times less potent than bupivacaine. The inhibition of KCNQ2/Q3 channels by bupivacaine resulted in a significant and reversible depolarization of the membrane potential. Retigabine (300 nm-10 microm) reversed the inhibitory action of bupivacaine on KCNQ2/Q3 channels as well as the depolarization of the membrane potential.<br />Conclusions: The anticonvulsant retigabine at nanomolar concentrations reverses the inhibitory effect of micromolar concentrations of bupivacaine. Our results allow the hypothesis that activation of KCNQ2/Q3 channels by retigabine may offer a novel therapeutic approach for the treatment of bupivacaine-induced seizures.
- Subjects :
- Anesthetics, Local toxicity
Animals
Bupivacaine toxicity
CHO Cells
Cricetinae
Humans
KCNQ2 Potassium Channel
KCNQ3 Potassium Channel
Kinetics
Membrane Potentials drug effects
Neurotoxicity Syndromes pathology
Patch-Clamp Techniques
Potassium Channels, Voltage-Gated
Carbamates pharmacology
Phenylenediamines pharmacology
Potassium Channels agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0003-3022
- Volume :
- 101
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Anesthesiology
- Publication Type :
- Academic Journal
- Accession number :
- 15277926
- Full Text :
- https://doi.org/10.1097/00000542-200408000-00024