School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
J Pain. 2011 May;12(5):600-9. doi: 10.1016/j.jpain.2010.11.005. Epub 2011 Feb 5.
Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy.
This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS.
肠易激综合征（IBS）主要表现为腹痛，是一种功能性肠病。本研究旨在研究新生期母鼠分离（NMS）后支配结肠的背根神经节（DRG）神经元兴奋性和电压门控钾（K+）通道活性的变化。通过 FAST DiI™ 标记鉴定的 NMS 大鼠结肠 DRG 神经元显示出比非处理（NH）大鼠更大的细胞大小。全细胞膜片钳记录显示，NMS 大鼠结肠 DRG 神经元表现出：1）去极化的静息膜电位；2）增加的输入电阻；3）明显降低的阈强度；4）在两倍阈强度下诱发的动作电位数量显著增加。全细胞电压钳记录显示，两组神经元均表现出瞬时 A 型（I(A)) 和延迟整流（I(K)) K+电流。与 NH 大鼠神经元相比，NMS 大鼠神经元的 I(K)平均密度显著降低。此外，NMS 大鼠结肠 DRG 神经元中 Kv1.2 的表达明显减少。这些结果表明，NMS 主要通过抑制 I(K)电流来增加结肠 DRG 神经元的兴奋性，这可能是 Kv1.2 表达下调和胞体肥大的结果。
本研究表明，IBS 模型大鼠 DRG 神经元中的延迟整流 K 电流和 Kv1.2 表达发生改变，这代表了 IBS 内脏痛觉和敏化的分子机制，提示 Kv1.2 作为治疗 IBS 的潜在靶点。
