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2006-12-08

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176905

Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+ channel in macrophages

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Recurs relacionat

https://doi.org/10.1074/jbc.M704724200

Resum

Voltage-dependent K(+) (Kv) currents in macrophages are mainly mediated by Kv1.3, but biophysical properties indicate that the channel composition could be different from that of T-lymphocytes. K(+) currents in mouse bone marrow-derived and Raw-264.7 macrophages are sensitive to Kv1.3 blockers, but unlike T-cells, macrophages express Kv1.5. Because Shaker subunits (Kv1) may form heterotetrameric complexes, we investigated whether Kv1.5 has a function in Kv currents in macrophages. Kv1.3 and Kv1.5 co-localize at the membrane, and half-activation voltages and pharmacology indicate that K(+) currents may be accounted for by various Kv complexes in macrophages. Co-expression of Kv1.3 and Kv1.5 in human embryonic kidney 293 cells showed that the presence of Kv1.5 leads to a positive shift in K(+) current half-activation voltages and that, like Kv1.3, Kv1.3/Kv1.5 heteromers are sensitive to r-margatoxin. In addition, both proteins co-immunoprecipitate and co-localize. Fluorescence resonance energy transfer studies further demonstrated that Kv1.5 and Kv1.3 form heterotetramers. Electrophysiological and pharmacological studies of different ratios of Kv1.3 and Kv1.5 co-expressed in Xenopus oocytes suggest that various hybrids might be responsible for K(+) currents in macrophages. Tumor necrosis factor-alpha-induced activation of macrophages increased Kv1.3 with no changes in Kv.1.5, which is consistent with a hyperpolarized shift in half-activation voltage and a lower IC(50) for margatoxin. Taken together, our results demonstrate that Kv1.5 co-associates with Kv1.3, generating functional heterotetramers in macrophages. Changes in the oligomeric composition of functional Kv channels would give rise to different biophysical and pharmacological properties, which could determine specific cellular responses.

Matèries

Canals de potassi, Metabolisme, Macròfags

Matèries (anglès)

Potassium channels, Metabolism, Macrophages

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

VICENTE GARCÍA, Rubén, ESCALADA, Artur, VILLALONGA, Núria, TEXIDÓ, Laura, ROURA-FERRER, Meritxell, MARTÍN SATUÉ, Mireia, LÓPEZ IGLESIAS, Carmen, SOLER PRAT, Concepció, SOLSONA SANCHO, Carles, TAMKUN, Michael m., FELIPE CAMPO, Antonio. Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+ channel in macrophages. _Journal of Biological Chemistry_. 2006. Vol. 281, núm. 49, pàgs. 37675-37685. [consulta: 25 de desembre de 2025]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/176905]

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