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Enhancement of delayed‐rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones
Author(s) -
Olschewski Andrea,
Wolff Matthias,
Bräu Michael E,
Hempelmann Gunter,
Vogel Werner,
Safronov Boris V
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704754
Subject(s) - chemistry , conductance , potassium channel , anesthesia , tetraethylammonium , patch clamp , bupivacaine , electrophysiology , biophysics , potassium , neuroscience , medicine , biology , physics , condensed matter physics , organic chemistry
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 μ M ) enhanced delayed‐rectifier K + current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μ M ). In isolated somata 0.1–10 μ M 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.British Journal of Pharmacology (2002) 136 , 540–549; doi: 10.1038/sj.bjp.0704754