Actions of general anaesthetics and arachidonic acid pathway inhibitors on K + currents activated by volatile anaesthetics and FMRFamide in molluscan neurones

1 K + currents activated by volatile general anaesthetics (I K(An) ) and by the neuropeptide FMRFamide (I K(FMRFa) ) were studied under voltage clamp in isolated identified neurones from the pond snail Lymnaea stagnalis . 2 I K(An) was activated by all the volatile anaesthetics studied. The maximal responses varied from agent to agent, with halothane≈sevoflurane>isoflurane>enflurane≈chloroform. 3 I K(An) was inhibited rather than activated by the n ‐alcohols from hexanol to dodecanol and by the 6‐ and 8‐carbon cycloalcohols. The n ‐alcohols exhibited a cutoff effect, with dodecanol being unable to half‐inhibit I K(An) . 4 Unlike I K(An) which did not desensitize at reasonable halothane concentrations, I K(FMRFa) desensitized at most FMRFamide concentrations studied. This desensitization could be substantially removed by halothane. Nonetheless, both I K(An) and I K(FMRFa) had similar sensitivities to the potassium channel blockers tetraethylammonium and 4‐aminopyridine, consistent with both currents flowing through the same channels. Responses to low concentrations of halothane and FMRFamide showed synergy. 5 The phospholipase A 2 inhibitor aristolochic acid inhibited I K(An) , consistent with a role for arachidonic acid (AA). The lipoxygenase and cyclooxygenase inhibitor nordihydroguaiaretic acid blocked I K(FMRFa) but did not affect I K(An) . I K(An) and I K(FMRFa) were little affected by the cyclooxygenase inhibitor indomethacin. These findings suggest that neither lipoxygenase nor cyclooxygenase pathways of AA metabolism are involved in the anaesthetic activation of I K(An) . 6 Inhibitors of a third, cytochrome P450‐mediated, pathway of AA metabolism (clotrimazole and econazole) potently blocked I K(An) , suggesting possible roles for certain cytochrome P450 isoforms in the activation of I K(An) .British Journal of Pharmacology (1998) 125 , 309–318; doi: 10.1038/sj.bjp.0702069