Involvement of potassium and calcium channels at the locus coeruleus in fentanyl-induced muscular rigidity in the rat.
Previous work from our laboratory suggested that Go alpha protein at the locus coeruleus (LC) may be involved in the signal transduction process that underlies muscular rigidity induced by fentanyl. The present study further evaluated the roles of K+ and L-type Ca2+ channels, gating of which is known to be associated with activation of Go alpha protein, in this process, using Sprague-Dawley rats anesthetized with ketamine. Bilateral microinjection into the LC of tetraethylammonium chloride (100 or 200 pmol), a K+ channel blocker, and S(-)-Bay K 8644 (0.5 nmol), a Ca2+ channel activator, produced significant antagonization of the EMG activation elicited by fentanyl (100 micrograms/kg, i.v.), as recorded from the sacrococcygeus dorsalis lateralis muscle. On the other hand, local application to the bilateral LC of diazoxide (10 or 20 nmol), an ATP-dependent K+ channel activator, and nifedipine (0.25 or 0.5 pmol), a L-type Ca2+ channel blocker, was ineffective in blunting fentanyl-induced muscular rigidity. These results suggest that activation of K+ channels and/or inhibition of L-type Ca2+ channels secondary to triggering of the Go alpha protein at the LC may underlie the signal transduction process in the mediation of fentanyl-induced muscular rigidity.
Lee
T Y
TY
Department of Anesthesiology, National Yang-Ming University, Taipei, Taiwan, ROC.
Fu
M J
MJ
Lui
P W
PW
Chan
S H
SH
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D003981:Diazoxide / Q000494:pharmacology; D004576:Electromyography; D005283:Fentanyl / Q000009:adverse effects*; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D000432:Methanol / Q000494:pharmacology; D009127:Muscle Rigidity / Q000139:chemically induced* / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D015221:Potassium Channels; D003981:Diazoxide; D005283:Fentanyl; D000432:Methanol