Fig. 10.

a Transmembrane movement of ions and water (blue dots) by the cotransporters NKCC1 and KCC2. Both use energy generated by the Na⁺/K⁺ pump. NKCC1 transports an inflow of 1K⁺, 1Na⁺, 2Cl⁻ with an estimated influx of 590 water molecules. KCC2 transports 1K⁺ and 1Cl⁻ outward with an estimated efflux of 500 water molecules. NKCC1 predominates in early development while KCC2 is the main Cl⁻ extruder (with water) in mature neurons. Figure by J. A. Hellas adapted from Chamma et al. [106]. b Schematic of the transport cycle of the proton-linked MCT, an example being L-lactate. The general translocation cycle shows the crypt-like action of a transporter moving water into a neuron. a1 The transporter is in an outward-open conformation (facing the ECS) where initial proton binding induces (a2) L-lactate binding along with water (blue dots). a3 The transporter changes to an inward-open conformation exposing its contents to the cytosol (into the ICS). a4 The proton is released into the cell, followed by L-lactate and water. a5, 6 The transporter returns to an outward-open conformation, the rate-limiting step in the cycle. Figure by J. A. Hellas interpreted from Halestrap’s description of MCT transport [107]. ATPase, adenosine triphosphatase, ATP, adenosine triphosphate, ECS, extracellular space, ICS, intracellular space, MCT, monocarboxylate transporter.