Enhancement of delayed-rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones.
Combining the patch-clamp recordings in slice preparation with the 'entire soma isolation' method we studied action of several local anaesthetics on delayed-rectifier K(+) currents in spinal dorsal horn neurones. Bupivacaine, lidocaine and mepivacaine at low concentrations (1 - 100 microM) enhanced delayed-rectifier K(+) current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 microM). In isolated somata 0.1 - 10 microM bupivacaine enhanced delayed-rectifier K(+) current by shifting its steady-state activation characteristic and the voltage-dependence of the activation time constant to more negative potentials by 10 - 20 mV. Detailed analysis has revealed that bupivacaine also increased the maximum delayed-rectifier K(+) conductance by changing the open probability, rather than the unitary conductance, of the channel. It is concluded that local anaesthetics show a dual effect on delayed-rectifier K(+) currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na(+) conductance only.
Olschewski
Andrea
A
Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-University, 35392 Giessen, Germany.
Wolff
Matthias
M
Bräu
Michael E
ME
Hempelmann
Gunter
G
Vogel
Werner
W
Safronov
Boris V
BV
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000737:chemistry / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008619:Mepivacaine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism
D000779:Anesthetics, Local; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; D008012:Lidocaine; D008619:Mepivacaine; D002045:Bupivacaine