title: Volume-sensitive chloride channels are involved in maintenance of basal cell volume in human acute lymphoblastic leukemia cells.
abstract: Chloride channels are expressed ubiquitously in different cells. However, the activation and roles of volume-activated chloride channels under normal isotonic conditions are not clarified, especially in lymphatic cells. In this study, the activation of basal and volume-activated chloride currents and their roles in maintenance of basal cell volume under isotonic conditions were investigated in human acute lymphoblastic leukemia Molt4 cells. The patch-clamp technique and time-lapse image analysis were employed to record whole-cell currents and cell volume changes. Under isotonic conditions, a basal chloride current was recorded. The current was weakly outward-rectified and volume-sensitive and was not inactivated obviously in the observation period. A 47% hypertonic bath solution and the chloride channel blockers NPPB and tamoxifen suppressed the current. Exposure of cells to 47% hypotonic bath solution activated further the basal current. The hypotonicity-activated current possessed properties similar to those of the basal current and was inhibited by NPPB, tamoxifen, ATP and hypertonic bath solution. Furthermore, extracellular hypotonic challenges swelled the cells and induced a regulatory volume decrease (RVD). Extracellular applications of NPPB, tamoxifen and ATP swelled the cells under isotonic conditions and inhibited the RVD induced by hypotonic cell swelling. The results suggest that some volume-activated chloride channels are activated under isotonic conditions, resulting in the appearance of the basal chloride current, which plays an important role in the maintenance of basal cell volume in lymphoblastic leukemia cells. Chloride channels can be activated further to induce a regulatory volume recovery when cells are swollen.
authors.affiliation: Department of Physiology of Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Cao
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.forename: Aihui
authors.initials: A
authors.lastname: Fan
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Linjie
authors.initials: L
authors.lastname: Yang
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009579:Nitrobenzoates / Q000494:pharmacology; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018118:Chloride Channels; D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D009579:Nitrobenzoates; D013629:Tamoxifen; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid