Stretch-inactivated cation channels: cellular targets for modulation of osmosensitivity in supraoptic neurons.

Rat magnocellular neurosecretory cells (MNCs) show an intrinsic sensitivity to acute changes in fluid osmolality. Experiments in acutely isolated supraoptic MNCs have shown that these responses are due to in part to the cell volume-dependent modulation of gadolinium-sensitive 33 pS stretch-inactivated cation (SIC) channels. Previous studies in vivo have shown that the slope (i.e. gain) of the 'osmosensory' relation between VP release and plasma osmolality can be increased or decreased under various physiological and pathological conditions. Here, we review recent work that shows how changes in external [Na] and excitatory neuropeptides such as angiotensin II (Ang II), cholecystokinin (CCK) and neurotensin (NT), may influence osmosensory gain in acutely isolated MNCs. Whole-cell and single-channel recording experiments have revealed that changes in external Na cause proportional changes in osmosensory gain as a result of modified SIC channel permeability and not by affecting mechanotransduction. In contrast, Ang II, CCK, or NT appear to convergently, and directly, stimulate the osmosensory cation conductance in MNCs. Preliminary analysis in current clamp further suggests that osmosensory gain may be increased upon exposure to these excitatory peptides. Whether such mechanisms contribute to the modulation of osmosensory gain in vivo remains to be established.