Ionic mechanism of action of a spin-labeled local anesthetic on squid axon membranes.
The ionic mechanism of action of a spin-labeled local anesthetic (SLA), 2-[N-methyl-N-(2,2,6,6-tetramethylpiperidonooxyl)]-ethyl 4-ethoxylbenzoate, was studied by means of voltage clamp technique with squid giant axons in comparison with the parent compound without spin label moiety, 2-(N,N-dimethyl)ethyl 4-ethoxylbenzoate (GS-01). Like other local anesthetics, they suppressed both sodium and potassium conductance increases. However, three remarkable differences have been noted between SLA and GS-01: (1) SLA is more effective than GS-01 in suppressing the sodium and potassium conductance increases; (2) SLA induces a potassium inactivation, whereas GS-01 is lacking this ability; (3) SLA has no effect on the time to peak sodium current, whereas GS-01 prolongs it. GS-01 resembles procaine with respect to (2) and (3) above. SLA will become a useful probe for the study of the molecular mechanism of local anesthetic aciton and of ionic channel function.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology*; D049832:Decapodiformes; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013113:Spin Labels
D000779:Anesthetics, Local; D001565:Benzoates; D010880:Piperidines; D013113:Spin Labels; D012964:Sodium; D011188:Potassium