IngentaConnect Amitriptyline Inhibits Voltage-Sensitive Sodium Currents in Rat G...

Authors: Bielefeldt K.¹; Ozaki N.²; Whiteis C.¹; Gebhart G.F.²

Source: Digestive Diseases and Sciences, Volume 47, Number 5, May 2002 , pp. 959-966(8)

Publisher: Springer

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 IC_50 of 20 mgr M. 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.

Keywords: gastric sensory neurons; sodium channels; vagal afferents; tricyclic antidepressants

Language: English

Document Type: Regular paper

Affiliations: 1: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA 2: Department of Pharmacology, University of Iowa, Iowa City, Iowa, USA

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Amitriptyline Inhibits Voltage-Sensitive Sodium Currents in Rat Gastric Sensory Neurons