Immunomodulation of voltage-dependent K+ channels in macrophages: molecular and biophysical consequences.

The Journal of General Physiology
Nuria VillalongaAntonio Felipe

Abstract

Voltage-dependent potassium (K(v)) channels play a pivotal role in the modulation of macrophage physiology. Macrophages are professional antigen-presenting cells and produce inflammatory and immunoactive substances that modulate the immune response. Blockage of K(v) channels by specific antagonists decreases macrophage cytokine production and inhibits proliferation. Numerous pharmacological agents exert their effects on specific target cells by modifying the activity of their plasma membrane ion channels. Investigation of the mechanisms involved in the regulation of potassium ion conduction is, therefore, essential to the understanding of potassium channel functions in the immune response to infection and inflammation. Here, we demonstrate that the biophysical properties of voltage-dependent K(+) currents are modified upon activation or immunosuppression in macrophages. This regulation is in accordance with changes in the molecular characteristics of the heterotetrameric K(v)1.3/K(v)1.5 channels, which generate the main K(v) in macrophages. An increase in K(+) current amplitude in lipopolysaccharide-activated macrophages is characterized by a faster C-type inactivation, a greater percentage of cumulative inactivation, and a mor...Continue Reading

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Citations

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Datasets Mentioned

BETA
M30441
AF302768
X00686

Methods Mentioned

BETA
PCR
Protein Assay
FCS
transfection

Software Mentioned

Phoretix
pClamp
PRISM
GraphPad

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