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CrossTalk proposal: Interstitial cells are involved and physiologically important in neuromuscular transmission in the gut

Traditional thinking has held that enteric motor neurons communicate with smooth muscle cells (SMCs) exclusively by volume transmission (Sarna, 2008). However, the neuromuscular apparatus of the gastrointestinal (GI) tract is complicated by the presence of interstitial cells of Cajal (ICC; KIT+ cells) and PDGFRα+ cells (cells labelled by antibodies against platelet-derived growth factor receptor α), which cluster along varicose fibres of motor neurons and form gap junctions with SMCs. The three types of cells form an electrical syncytium known (from the first letter of each of the three cell types) as the SIP syncytium (Sanders et al. 2012). SIP cells express receptors for motor neurotransmitters and respond to neurotransmitters. These observations suggest that interstitial cells are innervated by motor neurons and physiological responses of GI muscles are the integrated product of the SIP syncytium. ICC and PDGFRα+ cells lie in close proximity to varicosities of motor neurons in GI muscles. In the case of ICC, very close junctions (<20 nm) are common. Junctions of this sort have also been reported between varicosities and SMCs, but these appear less common (Daniel