Targeting Ion Channels: An Important Therapeutic Implication in Gastrointestinal Dysmotility in Patients With Spinal Cord Injury

Abstract

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.

Relaxant effects of Azadirachta indica A. Juss var. siamensis Valeton flower extract on isolated rat ileum contractions and the mechanisms of action

“…have suggested that release of neurotransmitters and several ion channels in GI tissues including ATP-sensitive potassium (K ATP ) channel, calcium ions (Ca 2+ )-activated potassium ions (K + ) channels, voltage-sensitive Ca 2+ channels and chloride ion channels play an important role in regulating GI motility. 4 In fact, those mechanisms have served as the fundamental knowledge in new discoveries and development of new therapeutic agents. Cholinergic agonists or laxative agents are widely used for gastrointestinal motility disorders management.…”

“…Cholinergic agonists or laxative agents are widely used for gastrointestinal motility disorders management. 4 However, these drugs have an undesirable side effect. Complementary and alternative medicines (CAM) have been associated with symptom management and quality of life in a common gastrointestinal disorder.…”

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

“…Mature ICCs, as shown by high levels of ramification, indicate more efficient ICCs [ 19 ]. In addition, neurotransmitters from enteric nerves activates ion channels in ICCs [ 12 ]. In the present study, ultrastructural assessment revealed significantly less colonic ICCs in SCI rats compared with sham animals.…”

“…Gastrointestinal motility is coregulated by the central and enteric nervous systems. Upon SCI, the connection between the defecation nerve center (sacral spinal cord; S 2–4 ) and central nerve center is lost, altering the normal function of the parasympathetic nerve system and damaging motor neurons in the enteric nervous system [ 12 ].…”

“…Many diseases related to abnormal gastrointestinal motility alter ICCs ultrastructure, distribution, and/or number [ 17 , 23 – 26 ]. Previous research pointed out that decreased activity of ICCs caused by SCI-induced enteric nervous dysfunction and may promote gastrointestinal dysmotility [ 12 , 18 ]. Nevertheless, whether intestinal c-kit expression changes after SCI is unknown.…”