Mechanosensitive channels may act as osmosensory transducers because osmotically evoked changes in cell volume alter forces applied to the channel and affect opening probability. However, osmotically stimulated cells regulate volume normally, whereas systemic osmoregulatory responses are sustained. Here we report that osmosensory neurons of rat supraoptic nucleus expressed significant membrane reserves, and could not regulate volume or total membrane surface area during osmotic perturbations, which may allow mechanosensitive channels to encode the amplitude and time course of an osmotic stimulus.