Radulovic Miroslav, Anand Preeti, Korsten Mark A, Gong Bing
Department of Medicine Icahn School of Medicine at Mount Sinai, New York, NY, USA.
National Center of Excellence for the Medical Consequences of SCI, James J Peters Veteran Affairs Medical Center, Bronx, NY, USA.
J Neurogastroenterol Motil. 2015 Oct 1;21(4):494-502. doi: 10.5056/jnm15061.
Gastrointestinal (GI) dysmotility is a severe, and common complication in patients with spinal cord injury (SCI). Current therapeutic methods using acetylcholine analogs or laxative agents have unwanted side effects, besides often fail to have desired effect. Various ion channels such as ATP-sensitive potassium (KATP) channel, calcium ions (Ca(2+))-activated potassium ions (K(+)) channels, voltage-sensitive Ca(2+) channels and chloride ion (Cl(-)) channels are abundantly expressed in GI tissues, and play an important role in regulating GI motility. The release of neurotransmitters from the enteric nerve terminal, innervating GI interstitial cells of Cajal (ICC), and smooth muscle cells (SMC), causes inactivation of K(+) and Cl(-) channels, increasing Ca(2+) influx into cytoplasm, resulting in membrane depolarization and smooth muscle contraction. Thus, agents directly regulating ion channels activity either in ICC or in SMC may affect GI peristalsis and would be potential therapeutic target for the treatment of GI dysmotility with SCI.
胃肠动力障碍是脊髓损伤（SCI）患者中一种严重且常见的并发症。目前使用乙酰胆碱类似物或泻药的治疗方法存在不良副作用，而且常常无法达到预期效果。各种离子通道，如ATP敏感性钾（KATP）通道、钙离子（Ca(2+)）激活的钾离子（K(+)）通道、电压敏感性Ca(2+)通道和氯离子（Cl(-)）通道，在胃肠道组织中大量表达，并在调节胃肠动力中发挥重要作用。从支配胃肠道Cajal间质细胞（ICC）和平滑肌细胞（SMC）的肠神经末梢释放的神经递质，会导致K(+)和Cl(-)通道失活，增加Ca(2+)流入细胞质，导致膜去极化和平滑肌收缩。因此，直接调节ICC或SMC中离子通道活性的药物可能会影响胃肠蠕动，并且可能成为治疗SCI所致胃肠动力障碍的潜在治疗靶点。
