The Significance of Interstitial Cells in Neurogastroenterology

Abstract

Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα + cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle Development and Maintenance of Differentiated Phenotype

“…Our Western blot data indicated that SRF levels increased after 2 weeks of partial obstruction but that MYH11 levels remained unchanged. 31,37 We found that each subtype was differentially remodeled during partial intestinal obstruction. However, further studies are needed to determine whether any of these subtypes can display plasticity in the remodeling response.…”

Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus

“…Although located very close to ICC, ultrastructural and functional aspects of FLCs are distinct from those of ICC[21]. Located very close to nerve endings, FLCs are considered to have a role in neurotransmission, especially within purinergic neurotransmission[37,38]. In this study, whereas a decrease in FLCs was observed in the gastric body and fundus of the DM group, no difference in the numbers of FLCs was observed in the antrum of the DM group compared to that of the control group.…”

The Role of Central and Enteric Nervous Systems in the Control of the Retrograde Giant Contraction

“…19 The ECA of the small intestine is primarily generated by interstitial cells of Cajal (ICC) located in the muscularis. 26 The ECA governs when a muscle contraction can occur. Contractions are possible when the membrane potential is in a depolarized state and is prevented when in a hyperpolarized state.…”