Recent Advances in Physiology of Osmosensitivity of Neurons

Presenter: David Cohen, MD (Oregon Health Sciences University)

Dr. Cohen began his lecture by showing us a slide of serum osmolarities among different species. What’s remarkable is that all the mammals on the slide have a serum osmolarity close to approximately 300. It would appear that the mechanisms used to regulate osmolarity are similar across mammals. The focus of the talk is on such mechanisms, mostly studied in animal models, with some crossover into our species.

The lamina terminalis (LT) is the key sensor of systemic osmolarity. It sits in the brain, just anterior to the third ventricle. Functional MRI images show that activity in the LT is increased when the sensation of thirst is present and when arginine vasopressin (AVP) is released. A number of receptors/channels sit in the LT, some of which were discussed in this lecture.

TRPV4 is the first channel protein that Dr. Cohen discussed. It is an osmosensor and in knockout mice, the loss of this channel leads to diminished thirst, water intake, and as a result, increases in serum osmolarity. In humans, the P19S polymorphism of the channel is present (TRPV4P19S). Its activity is also dependent on serum tonicity. A similar protein, TRPV1, is found in the LT and also has osmosensing characteristics. Knockout mice of this channel (TRPV1 -/-) suffer a similar fate as TRPV4 knockouts.

Additional channels still under investigation are NALCN and the NaX channels. The former is a non-selective cation channel in neurons that plays a role in maintaining serum Na+ in mice. The latter is a channel in glial cells (known as NaV2.1 in humans) that influences the appetite for sodium in mice.