title: High expression of large-conductance Ca2+-activated K+ channel in the CD133+ subpopulation of SH-SY5Y neuroblastoma cells.
abstract: Solid tumors contain a population of cancer stem cells (CSCs), and CD133 is widely used as a CSCs marker. We investigated the differences between CD133(+) and CD133(-) cells from the neuroblastoma cell line SH-SY5Y in terms of the expressions of voltage-gated ion channels. A CD133(+) enriched (>60%) population was isolated, and a subsequent whole-cell voltage-clamp study showed that these cells predominantly express TEA-sensitive outward K(+) currents (I(K,TEA)) and TTX-sensitive voltage-gated inward Na(+) currents (I(Na)). Cell-attached single channel recordings demonstrated higher density of large-conductance (155pS) channel in CD133(+) cells than in CD133(-) cells. The TEA-sensitivity and single channel conductance indicated the large-conductance Ca(2+)-activated K(+) channels (BK(Ca)). Furthermore, RT-PCR analysis of 22 transcripts of voltage-gated ion channels in SH-SY5Y cells showed the expressions of Cav1.3, Kir2.1, Kv1.4, Kv2.1, Kv4.2, Kv7.1, BK(Ca), and Nav1.7, and those of BK(Ca) and Nav1.7 were higher in CD133(+) than in CD133(-) cells. In addition, the increase of cytosolic Ca(2+) concentration ([Ca(2+)](c)) in response to ionomycin (a Ca(2+) ionophore) was higher and more sustained in CD133(+) than in CD133(-) cells. Plausibly membrane hyperpolarization via BK(Ca) might be responsible for the augmented Ca(2+) influx observed in CD133(+) cells. The physiological implications of the differential expression of BK(Ca) and Nav1.7 in CSCs require further investigation.
authors.affiliation: Institute Division of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Chung
authors.forename: Kyoung Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Choi
authors.forename: Yangmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyoung Sun
authors.initials: KS
authors.lastname: Park
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis*; D062556:NAV1.7 Voltage-Gated Sodium Channel; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D010455:Peptides / Q000032:analysis; D015222:Sodium Channels / Q000096:biosynthesis
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D062556:NAV1.7 Voltage-Gated Sodium Channel; C000606023:PROM1 protein, human; D010455:Peptides; C486866:SCN9A protein, human; D015222:Sodium Channels; D002118:Calcium