Electrophysiological effects of osmotic cell shrinkage in rat pancreatic β-cells.

Electrical and secretory activity in the pancreatic β-cell can be elicited by hypotonic cell swelling, due largely to activation of a volume-regulated anion channel (VRAC) leading to depolarisation and electrical activity. However, β-cell responses to cell shrinkage are less well characterised. The present study has examined the effects of osmotic cell shrinkage on rat pancreatic β-cells. Electrical activity and whole-cell current were studied in isolated β-cells using the perforated patch and conventional whole-cell recording techniques. Insulin release was measured using intact islets by radioimmunoassay. Exposure to a 33% hypertonic bath solution resulted in an initial depolarisation and a period of electrical activity. In several cases, this depolarisation was transient and was followed by a hyperpolarisation. A similar pattern was observed with insulin release. In voltage-clamp experiments, osmotic shrinkage resulted in activation of a non-selective cation channel (NSCC) sensitive to inhibition by flufenamic acid and Gd3+. It is suggested that activation of this NSCC is responsible for the depolarisation evoked by hypertonic media. The secondary hyperpolarisation is likely to be the result of inhibition of VRAC activity. These opposing ionic effects could underlie the biphasic effect on insulin release following exposure to hypertonic media.