DOWN-REGULATION OF VOLUME-ACTIVATED CL- CURRENTS DURING MUSCLE DIFFERENTIATION

We have used the whole cell configuration of the patch-clamp technique to investigate volume-activated Cl- currents in BC(3)H1 and C2C12 cel ls, two mouse muscle cell lines that can be switched from a proliferat ing to a differentiated musclelike state. Reducing the extracellular o smolality by 40% evoked large Cl- currents in proliferating BC(3)H1 an d C2C12 cells. These currents were outwardly rectifying and had an ani on permeability sequence as follows: I- > Br- > Cl- much greater than gluconate. They were inhibited by >50% by flufenamic acid (500 mu M), niflumic acid (500 mu M), and 5-nitro-2-(3-phenylpropylamino)benzoic a cid (100 mu M) but were relatively insensitive to tamoxifen (100 mu M) . A reduction in the serum concentration in the culture medium induced growth arrest in both cell lines, and the cells started to differenti ate into spindle-shaped nonfusing muscle cells (BC(3)H1) or myotubes ( C2C12). This differentiation was accompanied by a drastic decrease in the magnitude of the volume-activated Cl- currents. The close correlat ion between volume-activated Cl- currents and cell proliferation sugge sts that these currents may be involved in cell proliferation.