The use of the potassium channel activator riluzole to test whether potassium channels mediate the capacity of isoflurane to produce immobility.
Inhaled anesthetics produce immobility during noxious stimulation, primarily by actions on the spinal cord. In this study, we examined whether activation of potassium channels of the KCNK subfamily alters volatile anesthetic potency. We measured the change in isoflurane minimum alveolar anesthetic concentration (MAC) during 4-h intrathecal or IV infusions of the nonspecific KCNK activator riluzole in 54 Sprague-Dawley rats. IV or intrathecal infusions of riluzole doses that did not result in permanent injury or death equally decreased isoflurane MAC. We conclude that although riluzole exhibited anesthetic effects, the similar dose response from IV or intrathecal infusion suggests systemic absorption and actions in the brain rather than the spinal cord.


CONCLUSIONS
Riluzole, a drug that activates potassium channels and decreases glutamatergic neurotransmission, primarily acts on supraspinal sites to produce immobility in response to noxious stimuli. This finding does not support the hypothesis that potassium channels mediate the capacity of inhaled anesthetics to produce immobility in the face of noxious stimulation.
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005552:Forelimb / Q000502:physiology; D006614:Hindlimb / Q000502:physiology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009068:Movement / Q000187:drug effects*; D015221:Potassium Channels / Q000819:agonists* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000008:administration & dosage
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D015221:Potassium Channels; D019782:Riluzole; D007530:Isoflurane