IONIC SIGNALS IN T47D HUMAN BREAST-CANCER CELLS

Increasing evidence that ion channels play a key role in the modulatio n of cellular mitogenesis led us to investigate the membranes of T47D human breast cancer cells to identify the ion currents present. We rep ort here the results of voltage-clamp studies in the whole-cell config uration on isolated, non-synchronized single cells obtained from a duc tal breast carcinoma. In these studies we identified an outward rectif ying potassium current and a chloride current. The potassium current a ctivated at potentials more positive than -40 mV, reached an average v alue of 1.4 nA, and did not inactivate with time. This current was sen sitive to block by extracellular tetraethylammonium chloride (TEA, IC5 0 = 1 mu M), was insensitive to charybdotoxin (CTX, IC50 = 7.8 mu M), and was not diminished by repetitive pulses separated by 1 s. Rapid vo ltage-dependent inactivation of the current was demonstrated by tail c urrent analysis. The current appeared calcium-insensitive. Application of hyperpolarizing pulses did not elicit an inward potassium rectifie r current. Treatment with tetrodotoxin did not reveal the presence of an inward sodium current. The potassium current was increased by the p resence of aspartate in place of chloride and in the presence of the c hloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic ac id (DIDS). We conclude that currents present in T47D breast cancer cel ls include a chloride current and a voltage-gated potassium outward re ctifier. We suggest that the potassium current, either alone or in con junction with potassium currents reported in different human breast ca ncer cell lines by others, may play a role in the modulation of the ce ll cycle.