Figure 3.

A model of Ncc69 function in larval nerves, showing how the Na/K ATPase could create the need for solute removal from the extracellular space in larval nerves. The diagram shows a simplified view of the nerve, consisting of an axon and the subperineurial glia, whose septate junctions (SJ) restrict paracellular flow. The model leaves out two classes of glia whose roles are unknown: the wrapping glia, which are located inside the nerve, and the perineurial cells which are located on the outside. They are not essential in this model because they do not form septate junctions, and would not pose much of a barrier to paracellular ion flow. The ion flows in the diagram are represented by arrows. 1: The flow of ions is initiated by the action potential which leaves increased extracellular K in its wake through voltage-gated K channels. 2: In each cycle, the Na/K ATPase removes 2 K ions from the extracellular space, and replaces them with 3 Na ions. 3: Cl ions move to balance the gain in positive charge. These Cl ions could flow from other parts of the extracellular space and/or from intracellular sources, e.g., through Cl channels or transporters. The net effect of the Na/K ATPase is to accumulate NaCl in the extracellular space. If left unchecked (as in Ncc69 mutants), the accumulation of NaCl draws water into the extracellular space through osmosis, causing swelling. 4: Ncc69 relieves the pressure by transporting solutes into the subperineurial glia, causing it to swell. 5: The subperineurial cell exports solutes, presumably into the hemolymph, to maintain volume homeostasis. 6: K flows down the axoplasm to replace the K that is lost (From Leiserson et al. 2010 with permission.).