title: Amitriptyline inhibits voltage-sensitive sodium currents in rat gastric sensory neurons.
abstract: Recent studies indicate that peripheral mechanisms contribute to the analgesic effect of amitriptyline. We hypothesized that amitriptyline inhibits voltage-dependent sodium currents in gastric sensory neurons. To label gastric neurons, the stomach was exposed in male Sprague Dawley rats through a midline incision to inject the retrograde tracer DiI into the gastric wall. Seven days after surgery, nodose ganglia were harvested. Neurons were dissociated and cultured for 4-24 hr to record whole cell sodium currents with the patch-clamp technique. Amitriptyline reversibly inhibited voltage-sensitive sodium currents with an IC50 of 20 microM. At clinically relevant concentrations, the peak sodium current decreased by about 15%. This was associated with a slowed recovery from inactivation, leading to a significantly enhanced cumulative inhibition during brief repetitive depolarizations. These findings are consistent with a use-dependent block of voltage-dependent sodium channels by amitriptyline. This effect may contribute to the analgesic properties of tricyclic antidepressants.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bielefeldt
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ozaki
authors.forename: Carol
authors.initials: C
authors.lastname: Whiteis
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects*; D013270:Stomach / Q000294:innervation*
chemical_list: D018712:Analgesics, Non-Narcotic; D015222:Sodium Channels; D000639:Amitriptyline