Differential block of fast and slow inactivating tetrodotoxin-sensitive sodium channels by droperidol in spinal dorsal horn neurons.
BACKGROUND
Dorsal horn neurons of the spinal cord participate in neuronal pain transmission. During spinal and epidural anesthesia, dorsal horn neurons are exposed to local anesthetics and opioids. Droperidol is usually given with opioids to avoid nausea and vomiting. A recently developed method of "entire soma isolation" has made it possible to study directly the action of droperidol on different components of Na+ current in dorsal horn neurons.


METHODS
Using a combination of the whole-cell patch-clamp recording from spinal cord slices and the entire soma isolation method, we studied the direct action of droperidol on two types of Na+ currents in dorsal horn neurons of young rats.


RESULTS
The tetrodotoxin-sensitive Na+ current in isolated somata consisted of a fast inactivating (tauF, 0.5-2 ms; 80-90% of the total amplitude) and a slow inactivating (tauS, 6-20 ms; 10-20% of the total amplitude) component. Droperidol, at concentrations relevant for spinal and epidural anesthesia, selectively and reversibly suppressed the fast component with a half-maximum inhibiting concentration (IC50) of 8.3 microm. The slow inactivating component was much less sensitive to droperidol; the estimated IC50 value was 809 microm.


CONCLUSIONS
Droperidol selectively blocks fast Na+ channels, the fast and slow components of the Na+ current in dorsal horn neurons are carried through pharmacologically distinct types of Na+ channels, and the effects of droperidol differ from those of local anesthetics and tetrodotoxin, which equipotently suppress both components. Droperidol may be suggested as a pharmacologic tool for separation of different types of inactivating tetrodotoxin-sensitive Na+ channel.
Olschewski
A
A
Departments of Anesthesiology and Intensive Care Medicine and Physiology, Justus-Liebig-University, Giessen, Germany.
Bräu
M E
ME
Hempelmann
G
G
Vogel
W
W
Safronov
B V
BV
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D004329:Droperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D026941:Sodium Channel Blockers; D013116:Spinal Cord / Q000166:cytology; D013779:Tetrodotoxin / Q000494:pharmacology*
D000759:Adjuvants, Anesthesia; D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D008012:Lidocaine; D004329:Droperidol