Cell-cycle-dependent expression of the large Ca2+-activated K+ channels in breast cancer cells.
In a previous work, we have reported that the ionic nature of the outward current recorded in MCF-7 cells was that of a K+ current. In this study, we have identified a Ca2+-activated K+ channel not yet described in MCF-7 human breast cancer cells. In cells arrested in the early G1 (depolarized cells), increasing [Ca2+]i induced both a shift in the I-V curve toward more negative potentials and an increase in current amplitude at negative and more at positive potential. Currents were inhibited by r-iberiotoxin (r-IbTX, 50 nM) and charybdotoxin (ChTX, 50 nM). These data indicate that human breast cancer cells express large-conductance Ca2+-activated K+ (BK) channels. BK current-density increased in cells synchronized at the end of G1, as compared with those in the early G1 phase. This increased current-density paralleled the enhancement in BK mRNA levels. Blocking BK channels with r-IbTX, ChTX or both induced a slight depolarization in cells arrested in the early G1, late G1, and S phases and accumulated cells in the S phase, but failed to induce cell proliferation. Thus, the expression of the BK channels was cell-cycle-dependent and seems to contribute more to the S phase than to the G1 phase. However, these K+ channels did not regulate the cell proliferation because of their minor role in the membrane potential.
Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cédex, France. ha-sciences@u-picardie.fr
Halima
H
Ouadid-Ahidouch
Morad
M
Roudbaraki
Ahmed
A
Ahidouch
Philippe
P
Delcourt
Natalia
N
Prevarskaya
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D018999:Charybdotoxin / Q000494:pharmacology; D004553:Electric Conductivity; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000378:metabolism*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; C064719:iberiotoxin