Li S, Chen J D Z
Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA.
Neurogastroenterol Motil. 2014 Jul;26(7):962-70. doi: 10.1111/nmo.12350. Epub 2014 Apr 23.
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.
Male Sprague-Dawley rat pups at 10-day old received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days 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.
(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 ± 6.9 pA/pF), compared to that of control (93.1 ± 8.3 pA/pF). (3) Protein expression of KV 4.3 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.
尽管没有器质性结构异常的证据，但疼痛或不适是功能性消化不良的突出症状，被认为反映了内脏超敏反应，但其潜在机制尚不清楚。在此，我们研究了新生期胃刺激诱导的功能性消化不良大鼠模型中背根神经节（DRG）神经元的电生理特性和电压门控钾通道的表达。
10日龄雄性Sprague-Dawley大鼠幼崽通过口服灌胃给予0.1%碘乙酰胺（IA）或赋形剂，持续6天，并在成年后进行研究。收集经逆行示踪剂标记的胃特异性T8 - T12 DRG神经元，用于电压钳和电流钳模式下的膜片钳研究，并通过蛋白质印迹法检测T8 - T12 DRG中钾通道的蛋白质表达。
（1）与对照组相比，新生期IA处理的大鼠中，胃特异性而非非胃DRG神经元表现出兴奋性增强：静息膜电位去极化、动作电位（AP）激活的电流阈值降低以及对电流刺激的AP数量增加。（2）与对照组（93.1±8.3 pA/pF）相比，IA处理的大鼠中四乙铵不敏感电流（瞬时失活A型电流）的电流密度显著较小（65.4±6.9 pA/pF），而四乙铵敏感电流（缓慢失活延迟整流钾电流）则无显著差异。（3）IA处理的大鼠中KV 4.3的蛋白质表达下调。
在轻度新生期胃刺激的成年大鼠中，胃特异性DRG神经元中的A型钾通道显著下调，这在一定程度上导致DRG神经元兴奋性增强，进而导致胃超敏反应的发生。
