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 Gm protein at the loc us coeruleus (LC) may be involved in the signal transduction process t hat 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 mu g/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 Kt 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 trigg ering of the Go alpha protein at the LC may underlie the signal transd uction process in the mediation of fentanyl-induced muscular rigidity.