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 Goα 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 Goa 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 μg/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 Goa protein at the LC may underlie the signal transduction process in the mediation of fentanyl-induced muscular rigidity.