A SWELLING-ACTIVATED CHLORIDE CURRENT IN RAT SYMPATHETIC NEURONS

1. We have tested whether neurones show a swelling-induced Cl- current following hypotonic shock, by recording membrane current responses an d cell volume changes in voltage clamped isolated rat sympathetic neur ones during application of hypotonic solutions. 2. Using both whole-ce ll and perforated patch recording methods, hypotonic solution caused c ell swelling and the activation of an inward Cl- current at -6O MV. Th is current showed weak outward rectification with no obvious time depe ndence. It was inhibited by SITS (0.3-1mM), NPPB (30-300 mu M) and nif lumic acid (50-200 mu M), but not by tamoxifen (10 mu M). 3. Hypotonic solution did not cause a rise in intracellular Ca2+ concentration as measured by simultaneous indo-1 fluorescence. Also, neither the volume change nor Cl- current were affected by the removal of external Ca2or internal Ca2+ buffering to less than or equal to nM with EGTA. 4. T he Cl- current was unaffected by an inhibitor of protein kinase C (PKC ; GF109203X, 3 mu M) or by omission of ATP from the pipette solution. 5. Cells exhibited a regulatory volume decrease during sustained expos ure to hypotonic solution. This was completely inhibited by 0.5 mM nif lumic acid. 6. It is concluded that osmotic swelling induces an outwar dly rectifying, Ca2+- and PKC-independent Cl- current in these nerve c ells. It is suggested that this current may be involved in volume regu latory mechanisms.