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Subunit Expression in Macrophages Depends upon Proliferation and the Mode of Activation1
* Molecular Physiology Laboratory, Departament de Bioquímica i Biologia Molecular and
Departament de Fisiologia, Universitat de Barcelona, and
Macrophage Biology Group, Biomedical Research Institute of Barcelona, Barcelona, Spain;
Cellular and Molecular Neurobiology Laboratory, Departament de Biologia Cellular i Anatomia Patològica, Universitat de Barcelona-Campus de Bellvitge, Hospitalet de Llobregat, Spain; and
¶ Departments of Physiology and Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523
Voltage-dependent potassium channels (Kv) in leukocytes are involved in the immune response. In bone marrow-derived macrophages (BMDM), proliferation and activation induce delayed rectifier K+ currents, generated by Kv1.3, via transcriptional, translational, and posttranslational controls. Furthermore, modulatory Kv
subunits coassociate with Kv
subunits, increasing channel diversity and function. In this study we have identified Kv subunits in mouse BMDM, studied their regulation during proliferation and activation, and analyzed K+ current parameters influenced by these proteins. BMDM express all isoforms of Kv1 (Kv1.1, Kv1.2, and Kv1.3) and Kv2 (Kv2.1), but not Kv4, the alternatively spliced murine Kv3 variant. M-CSF-dependent proliferation induced all Kv isoforms. However, LPS- and TNF--induced activation differentially regulated these subunits. Although LPS increased Kv1.3, reduced Kv1.2, and maintained Kv1.1 mRNA levels constant, TNF- up-regulated Kv1.1, down-regulated Kv1.2, and left Kv1.3 expression unchanged. Moreover, in contrast to TNF-, M-CSF- and LPS- up-regulated Kv2.1. K+ currents from M-CSF- and LPS-stimulated BMDM exhibited faster inactivation, whereas TNF- increased 
values. Although in M-CSF-stimulated cells the half-inactivation voltage shifted to more positive potentials, the incubation with LPS and TNF- resulted in a hyperpolarizing displacement similar to that in resting BMDM. Furthermore, activation time constants of K+ currents and the kinetics of the tail currents were different depending upon the mode of activation. Our results indicate that differential Kv expression modifies the electrical properties of Kv in BMDM, dependent upon proliferation and the mode of activation. This could determine physiologically appropriate surface channel complexes, allowing for greater flexibility in the precise regulation of the immune response.
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