Figure 9.

Schematic diagram of the new concept based on this study. ARs are expressed on PDGFRα⁺ cells. Neuronal or hormonal NE or Epi, via binding to and activating α1A ARs in PDGFRα⁺ cells, opens SK3 channels through increasing intracellular [Ca²⁺] by inositol triphosphate (IP3) and hyperpolarize (Hyperpol) them. Hyperpolarization of PDGFRα⁺ cells is propagated to SMC via gap junctions (GJ) and inhibits contractions of them. α1D ARs are expressed by SMC. Neuronal or hormonal NE or Epi, via binding to and activating α1D ARs on SMC, can make myosin light chain kinase (MLCK) activated and SMC contract through activation of calmodulin (CM) via increase of intracellular [Ca²⁺] by IP3 or can activate Rho kinase pathway and inactivate myosin light chain phosphatase (MLCP), which leads to contractions of SMC. ICC might not express α1 ARs. ANO1, anoctamin-1, Ca²⁺ -activated Cl^– channels. Altogether, neuronal or hormonal NE or Epi can inhibit human colonic contractions via α1A AR-SK channel signaling pathway in PDGFRα⁺ cells and excite them via α1D AR on SMC.