A 23-PS CA-2+-ACTIVATED K+ CHANNEL IN MCF-7 HUMAN BREAST-CARCINOMA CELLS - AN APPARENT CORRELATION OF CHANNEL INCIDENCE WITH THE RATE OF CELL-PROLIFERATION

In studies on the apical membranes of cultured MCF-7 human breast carcinoma cells, we found two conspicuous K+ channel types with conductances of 23 and 70 pS, respectively. Of these, the 23-pS K+ channel was most conspicious. In cell-attached patches with KCl in the pipette, it had a linear current/voltage (I/V) relation and was activated by depolarisation and in excised inside-out patches it was highly selective for K+ over Na+ (permeability ratio of Na+ to K+, P(Na)/P(K) = 0.02). Rubidium (Rb+) had a similar permeability to K+, although it was only conducted at 20% of the rate of K+, and cesium (Cs+) had a permeability less than 30% that of K+ and was not conducted at all. Both Cs+ and Rb+ acted as partial blockers when applied internally but the channel was not blocked by external tetraethylammonium (TEA, 10 mmol/1), quinidine (200-mu-mol/l) or apamin (50 nmol/l). It was activated by Ca2+ in the range 10(-7) - 10(-6) mol/l. In cell-attached patches at a pipette potential of 0 mV, the open-time histogram was described by a single exponential (time constant 1.6 ms) and the closed-time histogram by two exponentials (time constants 0.5 and 1.5 ms). The incidence of the 23-pS but not the 70-pS channel depended on the rate of cell proliferation. Thus, in studies on cell-attached patches from cells in the exponential growth phase, the 23-pS channel was observed in 78% of patches. However, when the proliferation rate was decreased, whether as a result of allowing the monolayer to reach confluence, or of cell treatment with an anti-oestrogen (tamoxifen, 10-mu-mol/l), or a phorbol ester [phorbol 12-myristate 13-acetate (TPA), 2.6 nmol/l], the channel incidence was reduced to 42%, 60% and 42%, respectively. The activity of the 23-pS channel is not obligatory for cell division, however, since the rate of cell proliferation remained the same in MCF-7 cultures in which the channel was not expressed.