Activation of calcium channel by shear-stress in cultured renal distal tubule cells.

Using the patch-clamp technique and the fura-2 fluorescence measurement, we found that flow of a normal solution simultaneously increased both the inward cation (Ca) currents and the cytosolic Ca activity (Cai) in cultured renal distal tubule cells (A6 cells). The activation of these signals was voltage-independent and required a lag period of about 30 s. Flow of a Ca free solution (plus 0.1-0.5 mM EGTA) failed to increase these signals. The Ca current increased and saturated with increasing extracellular Ca concentrations (apparent Km, 1 mM Ca; maximum Ca current, 43 pA). Ni (1 mM) and La (1 mM) inhibited the flow-induced Cai-increase, but nicardipine (50 microM) did not. These results strongly suggest that in A6 cells flow increases Ca-influx through a shear-stress activated Ca-channel and may regulate the cellular transport functions.