0541. Aquaporins and the brain

One of the most exciting and important pieces of research in recent years has been the identification and categorization of aquaporins in humans, plants and microbes. While science has long been aware of water's movement through tissues by osmosis, the physiology and pathophysiology of various tissues and organs indicated that there also had to be a mechanism for rapid transport of large amounts of water. The aquaporins are large, complex, protein molecules found in membranes and structured in such a way that they are specific for water (and some for glycerol). Aquaporin 4 (AQP4) is the major water channel in the central nervous system. It is expressed at fluid-tissue barriers in brain and cord. AQP4-deficient mice have reduced effects of water permeability; as such they are better able to withstand ischaemic brain insults but less able to withstand vasogenic insults that result in oedema. Researchers have also established a link between AQP4 anchoring to hippocampal perivascular astrocyte endfoot membranes and temporal lobe epilepsy. This anchoring is dependent on dystrophin which is reduced in these areas in TLE. The postulate is that as a result of the latter there is less AQP4 in these hippocampal areas, perturbed water flux through the astrocytes, impaired buffering of extracellular potassium, and a resultant propensity for seizures. All this is very preliminary work and we can expect to read much more as scientists unravel where and how these proteins influence water movement and concentrations of various substances, relationships to disease states, if and how current treatments affect the AQPs, and what drugs need to be developed to modify harmful situations and processes.
Read more:
Neuroscience 2004; 129: 983-91
Proc Natl Acad Sci USA 2005; 102: 1193-8
Epilepsy Curr 2005; 5: 104-6