Transport-coupling hypothesis of tubuloglomerular feedback signal transmission

A mathematical model was used to explore the transport-coupling hypothesis of tubuloglomerular feedback (TGF) signal transmission from the macula densa (MD) to the extraglomerular mesangium (EGM) within the juxtaglomerular apparatus (JGA). The transport-coupling hypothesis supposes that changes in MD transport alter the ionic composition of the EGM interstitium, thereby stimulating the Goormaghtigh cells. This hypothesis is based on the avascularity of the EGM and the presence of a narrow cleft (JGA cleft) between the MD and Goormaghtigh cells. The model describes NaCl and water transport by MD cells and mass conservation in the JGA cleft. It calculates cleft water flow and NaCl concentration [( NaCl]). If the cleft is narrow, the model predicts that cleft [NaCl] will vary directly with luminal [NaCl] and net MD NaCl transport. With strong active NaCl transport, the MD cell plaque may act as an ionic amplifier, in that small changes in luminal [NaCl] might elicit much larger concentration changes within the cleft. Even without active NaCl transport, cleft [NaCl] could remain coupled to luminal [NaCl] if the MD cells passively secrete NaCl. With high hydraulic conductivity, cleft [NaCl] also varies with luminal osmolarity. With a wide cleft, a low diffusional resistance of the EGM interstitium, or swollen MD lateral intercellular spaces, the transport coupling between cleft and luminal [NaCl] is markedly attenuated. The predictions of our model of large changes in JGA interstitial composition agree well with published measurements made in Amphiuma. However, the low Na+-K+-ATPase content and high water permeability of mammalian MD suggest that the transport-coupling effects in mammals may be significantly less pronounced than in Amphiuma.