title: BKCa channels activating at resting potential without calcium in LNCaP prostate cancer cells.
abstract: Large-conductance Ca2+-dependent K+ (BK(Ca)) channels are activated by intracellular Ca2+ and membrane depolarization in an allosteric manner. We investigated the pharmacological and biophysical characteristics of a BK(Ca)-type K+ channel in androgen-dependent LNCaP (lymph node carcinoma of the prostate) cells with novel functional properties, here termed BK(L). K+ selectivity, high conductance, activation by Mg2+ or NS1619, and inhibition by paxilline and penitrem A largely resembled the properties of recombinant BK(Ca) channels. However, unlike conventional BK(Ca) channels, BK(L) channels activated in the absence of free cytosolic Ca2+ at physiological membrane potentials; the half-maximal activation voltage was shifted by about -100 mV compared with BK(Ca) channels. Half-maximal Ca2+-dependent activation was observed at 0.4 microM: for BK(L) (at -20 mV) and at 4.1 microM: for BK(Ca) channels (at +50 mV). Heterologous expression of hSlo1 in LNCaP cells increased the BK(L) conductance. Expression of hSlo-beta1 in LNCaP cells shifted voltage-dependent activation to values between that of BK(L) and BK(Ca) channels and reduced the slope of the P (open) (open probability)-voltage curve. We propose that LNCaP cells harbor a so far unknown type of BK(Ca) subunit, which is responsible for the BK(L) phenotype in a dominant manner. BK(L)-like channels are also expressed in the human breast cancer cell line T47D. In addition, functional expression of BK(L) in LNCaP cells is regulated by serum-derived factors, however not by androgens.
authors.affiliation: Institute of Molecular Cell Biology, Molecular and Cellular Biophysics, Friedrich Schiller University , Jena, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Gessner
authors.forename: K
authors.initials: K
authors.lastname: Schönherr
authors.forename: M
authors.initials: M
authors.lastname: Soom
authors.forename: A
authors.initials: A
authors.lastname: Hansel
authors.forename: M
authors.initials: M
authors.lastname: Asim
authors.forename: A
authors.initials: A
authors.lastname: Baniahmad
authors.forename: C
authors.initials: C
authors.lastname: Derst
authors.forename: T
authors.initials: T
authors.lastname: Hoshi
authors.forename: S H
authors.initials: SH
authors.lastname: Heinemann
mesh_terms: D002118:Calcium / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000503:physiopathology*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium