tetrodotoxin and Gastritis

Voltage-dependent Na+ currents are important determinants of excitability. We hypothesized that gastric inflammation alters Na+ current properties in primary sensory neurons.. The stomach was surgically exposed in rats to inject the retrograde tracer 1.1'-dioctadecyl-3,3,3,'3-tetramethylindocarbocyanine methanesulfonate and saline (control) or 20% acetic acid (ulcer group) into the gastric wall. Nodose or thoracic dorsal root ganglia (DRG) were harvested after 7 days to culture neurons and record Na+ currents using patch clamp techniques.. There were no lesions in the control and 3 +/- 1 ulcers in the ulcer group. Na+ currents recovered significantly more rapidly from inactivation in nodose and DRG neurons obtained from animals in the ulcer group compared with controls. This was partially a result of an increase in the relative contribution of the tetrodotoxin-resistant to the peak sodium current. In addition, the recovery kinetics of the tetrodotoxin-sensitive current were faster. In DRG neurons, gastric inflammation shifted the voltage-dependence of activation of the tetrodotoxin-resistant current to more hyperpolarized potentials.. Gastric injury alters the properties of Na+ currents in gastric sensory neurons. This may enhance excitability, thereby contributing to the development of dyspeptic symptoms.

Topics: Acetic Acid; Anesthetics, Local; Animals; Disease Models, Animal; Ganglia, Spinal; Gastritis; Hyperalgesia; Ion Channel Gating; Male; Membrane Potentials; Neurons, Afferent; Nodose Ganglion; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Sodium; Sodium Channels; Stomach; Stomach Ulcer; Tetrodotoxin

Visceral hypersensitivity can be found in more than one third of patients with dyspeptic symptoms. We hypothesized that peripheral sensitization plays an important role in the development of hypersensitivity.. We induced mild gastritis in Sprague-Dawley rats by adding 0.1% iodoacetamide to the drinking water. The stomach was injected with a retrograde label to identify gastric sensory neurons. Nodose and T9, T10 dorsal root ganglia were removed 7 days after initiation of iodoacetamide treatment. The cells were dissociated and cultured for 3-8 hours before recording whole cell currents using the patch-clamp technique.. Iodoacetamide induced a mild gastritis. Although there were no changes in voltage-sensitive inward and outward currents in nodose neurons, the inward currents increased significantly in T9, T10 spinal neurons. A more detailed analysis of sodium currents showed that this was caused by an increase in the tetrodotoxin-resistant sodium current.. Mild gastritis increases the tetrodotoxin-resistant current in gastric spinal sensory neurons. Considering the importance of sodium currents as determinants of neuron excitability, this change may contribute to peripheral sensitization and enhanced neuron excitability.

Topics: Alkylating Agents; Anesthetics, Local; Animals; Cells, Cultured; Electrophysiology; Ganglia, Spinal; Gastritis; Iodoacetamide; Male; Membrane Potentials; Neurons, Afferent; Rats; Rats, Sprague-Dawley; Sodium; Sodium Channels; Stomach; Tetrodotoxin