Down-regulation of A-type potassium channel in gastric-specific DRG neurons in a rat model of functional dyspepsia

Background Although without evidence of organic structural abnormalities, pain or discomfort is a prominent symptom of functional dyspepsia and considered to reflect visceral hypersensitivity whose underlying mechanism is poorly understood. Here, we studied electrophysiological properties and expression of voltage-gated potassium channels in dorsal root ganglion (DRG) neurons in a rat model of functional dyspepsia induced by neonatal gastric irritation. Methods Male Sprague-Dawley rat pups at 10-day old received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6days and studied at adulthood. Retrograde tracer-labeled gastric-specific T8-T12 DRG neurons were harvested for the patch-clamp study in voltage and current-clamp modes and protein expression of K+ channel in T8-T12 DRGs was examined by western blotting. Key Results (1) Gastric specific but not non-gastric DRG neurons showed an enhanced excitability in neonatal IA-treated rats compared to the control: depolarized resting membrane potentials, a lower current threshold for action potential (AP) activation, and an increase in the number of APs in response to current stimulation. (2) The current density of tetraethylammonium insensitive (transiently inactivating A-type current), but not the tetraethylammonium sensitive (slow-inactivating delayed rectifier K+ currents), was significantly smaller in IA-treated rats (65.4 +/- 6.9pA/pF), compared to that of control (93.1 +/- 8.3pA/pF). (3) Protein expression of KV4.3 was down-regulated in IA-treated rats. Conclusions & Inferences A-type potassium channels are significantly down-regulated in the gastric-specific DRG neurons in adult rats with mild neonatal gastric irritation, which in part contribute to the enhanced DRG neuron excitabilities that leads to the development of gastric hypersensitivity.