Osmo- and mechanosensitivity of the transient outward K+ current in a mammalian neuronal cell line.

1. The transient outward current in NG108-15 cells was investigated with the whole-cell patch-clamp technique. The current was inhibited by external 4-aminopyridine or tetra-ethylammonium. The reversal potential shifted rightward with increased external K+ concentrations. 2. Current inactivation was markedly accelerated in hyperosmotic media (+30 mosmol l-1) and after nearby ejection of isosmotic solution with maximal acceleration occurring after 15-20 s and full recovery within 2-4 min, thus demonstrating an osmo- and mechanosensitivity of this current. Voltage-dependent Na+ and Ca2+ currents were unaffected. 3. Hyperosmotic solution shifted the voltage dependence of inactivation leftward. Inactivation was sensitive to reducing and oxidizing intracellular conditions. Reduction blocked the acceleration of current inactivation induced by hyperosmotic media, while oxidation did not hamper the response. 4. Action potentials had a decreased amplitude and a slower repolarization after hyperosmotic ejections. 5. It is concluded that the transient K+ current is osmo- and mechanosensitive, thus providing a mechanism for extracellular osmolarity to modulate neuronal excitability. The response appeared to be mediated through a changed sensitivity of the inactivating principle to the membrane electric field and was dependent on the redox state of the cell.