title: Interaction of alfaxalone with the neuronal and the skeletal muscle sodium channel.
abstract: The neurosteroid alfaxalone exerts potent anesthetic activity in humans and animals. In former studies on myelinated axons, alfaxalone was assumed to produce a local anesthetic-like effect on the peripheral nervous system. Therefore,the present in vitro study aimed to characterize possible modulatory actions of alfaxalone on voltage-gated sodium channels. -Subunits of voltage-gated neuronal (Nav1.2)and skeletal muscle (Nav1.4) sodium channels were stably expressed in human embryonic kidney cells, and in vitro effects of alfaxalone were compared with lidocaine by means of the patch clamp technique. Alfaxalone preferentially blocked slow inactivated channels and therefore could provide membrane-stabilizing effects in ischemic/hypoxic tissues where slow inactivation is regarded to play a crucial role.
authors.affiliation: Clinic for Anaesthesia and Critical Care Medicine, Veterinary School of Medicine, Hannover, Germany.
authors.forename: Nilufar
authors.initials: N
authors.lastname: Foadi
authors.forename: Igor
authors.initials: I
authors.lastname: Pilawski
authors.forename: Vanessa
authors.initials: V
authors.lastname: Buchholz
authors.forename: Jeanne
authors.initials: J
authors.lastname: de la Roche
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
authors.forename: Andreas
authors.initials: A
authors.lastname: Leffler
authors.forename: Jörg
authors.initials: J
authors.lastname: Ahrens
authors.forename: Sabine
authors.initials: S
authors.lastname: Kästner
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D018482:Muscle, Skeletal / Q000502:physiology; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011277:Pregnanediones / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D000777:Anesthetics; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011277:Pregnanediones; C568251:SCN2A protein, human; C106251:SCN4A protein, human; D015222:Sodium Channels; C006477:alphaxalone