Suppression of potassium conductance by droperidol has influence on excitability of spinal sensory neurons.
BACKGROUND
During spinal and epidural anesthesia with opioids, droperidol is added to prevent nausea and vomiting. The mechanisms of its action on spinal sensory neurons are not well understood. It was previously shown that droperidol selectively blocks a fast component of the Na+ current. The authors studied the action of droperidol on voltage-gated K+ channels and its effect on membrane excitability in spinal dorsal horn neurons of the rat.


METHODS
Using a combination of the patch-clamp technique and the "entire soma isolation" method, the action of droperidol on fast-inactivating A-type and delayed-rectifier K+ channels was investigated. Current-clamp recordings from intact sensory neurons in spinal cord slices were performed to study the functional meaning of K+ channel block for neuronal excitability.


RESULTS
Droperidol blocked delayed-rectifier K+ currents in isolated somata of dorsal horn neurons with a half-maximum inhibiting concentration of 20.6 microm. The A-type K+ current was insensitive to up to 100 microm droperidol. At droperidol concentrations insufficient for suppression of an action potential, the block of delayed-rectifier K+ channels led to an increase in action potential duration and, as a consequence, to lowering of the discharge frequency in the neuron.


CONCLUSIONS
Droperidol blocks delayed-rectifier K+ channels in a concentration range close to that for suppression of Na+ channels. The block of delayed-rectifier K+ channels by droperidol enhances the suppression of activity in spinal sensory neurons at drug concentrations insufficient for complete conduction block.
Olschewski
A
A
Department of Anesthesiology and Intensive Care Medicine and Physiology, Justus-Liebig-University, Giessen, Germany.
Hempelmann
G
G
Vogel
W
W
Safronov
B V
BV
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004329:Droperidol / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D014150:Antipsychotic Agents; D015221:Potassium Channels; D015222:Sodium Channels; D013779:Tetrodotoxin; D004329:Droperidol