The systemic inflammatory response is involved in the regulation of K(+) channel expression in brain via TNF-alpha-dependent and -independent pathways.
TNF-alpha, generated during the systemic inflammatory response, triggers a wide range of biological activities that mediate the neurologic manifestations associated with cancer and infection. Since this cytokine regulates ion channels in vitro (especially Kv1.3 and Kir2.1), we aimed to study Kv1.3 and Kir2.1 expression in brain in response to in vivo systemic inflammation. Cancer-induced cachexia and LPS administration increased plasma TNF-alpha. Kv1.3 and Kir2.1 expression was impaired in brain during cancer cachexia. However, LPS treatment induced Kv1.3 and downregulated Kir2.1 expression, and TNF-alpha administration mimicked these results. Experiments using TNF-alpha double receptor knockout mice demonstrated that the systemic inflammatory response mediates K(+) channel regulation in brain via TNF-alpha-dependent and -independent redundant pathways. In summary, distinct neurological alterations associated with systemic inflammation may result from the interaction of various cytokine pathways tuning ion channel expression in response to neurophysiological and neuroimmunological processes.
Vicente
Rubén
R
Molecular Physiology Laboratory, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, E-08028 Barcelona, Spain.
Coma
Mireia
M
Busquets
Silvia
S
Moore-Carrasco
Rodrigo
R
López-Soriano
Francisco J
FJ
Argilés
Josep M
JM
Felipe
Antonio
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D002100:Cachexia / Q000235:genetics / Q000503:physiopathology; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D051664:Kv1.3 Potassium Channel; D008114:Liver Neoplasms, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015703:Antigens, CD; C496974:Kcna3 protein, mouse; C496975:Kcna3 protein, rat; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha