Membrane stretch: a physiological stimulator of Ca2+-activated K+ channels in thick ascending limb.

The effects of membrane stretch on Ca2+-activated (maxi) K+ channels were examined in the apical membrane of cultured medullary thick ascending limb (MTAL) cells. Using cell-attached patchclamp technique, we found that negative pressure (-33 +/- 5 cmH2O) applied to the patch membrane increased fractional open probability (NPo) from 0.3 +/- 0.2 to 29.9 +/- 7.6% (n = 12) in the presence of 1.8 mM Ca2+ in the pipette. The activity returned to control on releasing the negative pressure. Reduction of extracellular osmolality from 293.2 +/- 1.6 to 219.8 +/- 1.1 mosmol/kg also activated K+ channels (NPo = 43.8 +/- 12.2%, n = 8) in cell-attached patches. Removal of Ca2+ from both pipette and bathing solution inhibited osmotic activation of K+ channels. K+ channels were shown to be Ca2+-activated K+ channels by their conductance (146 +/- 7 pS, n = 5) and Ca2+ dependence. Our data suggest that membrane stretch caused by swelling or possibly by tubular flow enhances Ca2+ entry across the apical cell membrane of MTAL cells activating maxi K+ channels.