4.4 Article

Amitriptyline inhibits voltage-sensitive sodium currents in rat gastric sensory neurons

期刊

DIGESTIVE DISEASES AND SCIENCES
卷 47, 期 5, 页码 959-966

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SPRINGER
DOI: 10.1023/A:1015061317793

关键词

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

资金

  1. NIDDK NIH HHS [DK01548] Funding Source: Medline
  2. NINDS NIH HHS [NS 35790] Funding Source: Medline

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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 muM. 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.

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