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2003-11-21

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176965

Differential voltage-dependent K+ channel responses during proliferation and activation in macrophages

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https://doi.org/10.1074/jbc.M304388200

Resum

Voltage-dependent K+ channels (VDPC) are expressed in most mammalian cells and involved in the proliferation and activation of lymphocytes. However, the role of VDPC in macrophage responses is not well established. This study was undertaken to characterize VDPC in macrophages and determine their physiological role during proliferation and activation. Macrophages proliferate until an endotoxic shock halts cell growth and they become activated. By inducing a schedule that is similar to the physiological pattern, we have identified the VDPC in non-transformed bone marrow-derived macrophages and studied their regulation. Patch clamp studies demonstrated that cells expressed outward delayed and inwardly rectifying K+ currents. Pharmacological data, mRNA, and protein analysis suggest that these currents were mainly mediated by Kv1.3 and Kir2.1 channels. Macrophage colony-stimulating factor-dependent proliferation induced both channels. Lipopolysaccharide (LPS)-induced activation differentially regulated VDPC expression. While Kv1.3 was further induced, Kir2.1 was down-regulated. TNF-alpha mimicked LPS effects, and studies with TNF-alpha receptor I/II double knockout mice demonstrated that LPS regulation mediates such expression by TNF-alpha-dependent and -independent mechanisms. This modulation was dependent on mRNA and protein synthesis. In addition, bone marrow-derived macrophages expressed Kv1.5 mRNA with no apparent regulation. VDPC activities seem to play a critical role during proliferation and activation because not only cell growth, but also inducible nitric-oxide synthase expression were inhibited by blocking their activities. Taken together, our results demonstrate that the differential regulation of VDPC is crucial in intracellular signals determining the specific macrophage response.

Matèries

Macròfags, Fisiologia, Canals de potassi

Matèries (anglès)

Macrophages, Physiology, Potassium channels

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Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

VICENTE GARCÍA, Rubén, ESCALADA, Artur, COMA, Mireia, FUSTER ORELLANA, Gemma, SÁNCHEZ TILLÓ, Ester, LÓPEZ IGLESIAS, Carmen, SOLER PRAT, Concepció, SOLSONA SANCHO, Carles, CELADA COTARELO, Antonio, FELIPE CAMPO, Antonio. Differential voltage-dependent K+ channel responses during proliferation and activation in macrophages. _Journal of Biological Chemistry_. 2003. Vol. 278, núm. 47, pàgs. 46307-46320. [consulta: 25 de febrer de 2026]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/176965]

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