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.
Ouadid-Ahidouch
Halima
H
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
Roudbaraki
Morad
M
Ahidouch
Ahmed
A
Delcourt
Philippe
P
Prevarskaya
Natalia
N
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