Potassium channels (KCh) have an important role on a number of physiological functions in mammalian cells. KCh are responsible for membrane excitability, secretion, activation and cell volume control among others (Felipe et al. 1993; Hille, 2001). Here we have studied the voltage-gated potassium channels and their regulatory subunits in bone marrow-derived macrophages (BMDM) to analyse their role in proliferation and activation. Macrophages originate from undifferentiated stem cells in the bone marrow and through the blood reach the different tissues and in most cases they undergo apoptosis. In response to the macrophage-colony stimulating factor (MCSF), macrophages are able to proliferate (Soler et al. 2001a). However, to carry out their functional activities, they must become activated. Lipopolysaccharide (LPS) is an activator of macrophages and it is also a potent apoptotic agent (Soler et al. 2001b).

We used BMDM isolated from mice as previously described (Soler et al. 2001a). Patch-clamp studies demonstrate that cells expressed outward delayed-rectifier and an inward rectifier K⁺ currents. Pharmacological studies indicated that the outward current was generated by Kv1.3. In addition, Kir 2.1 was responsible for the inward rectifier K⁺ current. Macrophages also express gene products from Kvβ1 and Kvβ2 modulatory subunits. MCSF-dependent proliferation induces both KCh and Kvβ auxiliary subunits in a time-dependent manner. These results were supported by an increase in KCh gene expression. When macrophages were activated with LPS, which stops proliferation, the KCh activity changed. While Kv1.3 further increased, Kir2.1 was down-regulated. Kvβ1 subunit gene products were differentially expressed and the Kvβ2.1 was up-regulated suggesting an increase in the amount and stability of the α/β membrane complex after LPS activation.

Our results describe for the first time the KCh and the Kvβ regulatory subunits present in BMDM. Proliferation is related to an overall increase in KCh activity and expression. However, activation induces a selective KCh differential regulation that could play a critical role to reach the immunitary response against infection.

This work was supported by MCYT, Spain (BFI2002-00764) and the University of Barcelona.