The Role of Ion Channels in Functional Gastrointestinal Disorders (FGID): Evidence of Channelopathies and Potential Avenues for Future Research and Therapeutic Targets.
Fatima MaqoudDomenico TricaricoRosanna MallamaciAntonella OrlandoFrancesco RussoPublished in: International journal of molecular sciences (2023)
Several gastrointestinal (GI) tract abnormalities, including visceral hypersensitivity, motility, and intestinal permeability alterations, have been implicated in functional GI disorders (FGIDs). Ion channels play a crucial role in all the functions mentioned above. Hormones and natural molecules modulate these channels and represent targets of drugs and bacterial toxins. Mutations and abnormal functional expression of ion channel subunits can lead to diseases called channelopathies. These channelopathies in gastroenterology are gaining a strong interest, and the evidence of co-relationships is increasing. In this review, we describe the correlation status between channelopathies and FGIDs. Different findings are available. Among others, mutations in the ABCC7 /CFTR gene have been described as a cause of constipation and diarrhea. Mutations of the SCN5A gene are instead associated with irritable bowel syndrome. In contrast, mutations of the TRPV1 and TRPA genes of the transient receptor potential (TRP) superfamily manifest hypersensitivity and visceral pain in sensory nerves. Recently, mice and humans affected by Cantu syndrome (CS), which is associated with the mutations of the KCNJ8 and ABCC9 genes encoding for the Kir6.1 and SUR2 subunits, showed dysfunction of contractility throughout the intestine and death in the mice after the weaning on solid food. The discovery of a correlation between channelopathies and FIGD opens new avenues for discovering new direct drug targets for specific channelopathies, leading to significant implications for diagnosing and treating functional GI diseases.
Keyphrases
- human health
- risk assessment
- irritable bowel syndrome
- genome wide identification
- genome wide
- cystic fibrosis
- copy number
- drug induced
- insulin resistance
- neuropathic pain
- poor prognosis
- magnetic resonance imaging
- pain management
- small molecule
- high fat diet induced
- gene expression
- chronic pain
- genome wide analysis
- spinal cord injury
- binding protein
- type diabetes
- metabolic syndrome
- high throughput
- long non coding rna
- skeletal muscle
- transcription factor
- current status
- intensive care unit
- adverse drug
- cerebral ischemia