The effects of Shaker β-subunits on the human lymphocyte K+ channel Kv1.3

The activation of T-lymphocytes is dependent upon, and accompanied by, an increase in voltage-gated K+ conductance. Kv1.3, a Shaker family K+ channel protein, appears to play an essential role in the activation of peripheral human T cells. Although Kv1.3-mediated K+ currents increase markedly during the activation process in mice, and to a lesser degree in humans, Kv1.3 mRNA levels in these organisms do not, indicating posttranscriptional regulation. In other tissues Shaker K+ channel proteins physically associate with cytoplasmic beta-subunits (Kv beta 1-3). Recently it has been shown that Kv beta 1 and Kv beta 2 are expressed in mouse T cells and that they are up-regulated during mitogen-stimulated activation. In this study, we show that the human Kv beta subunits substantially increase K+ current amplitudes when coexpressed with their Kv1.3 counterpart, and that unlike in mouse, protein levels of human Kv beta 2 remain constant upon activation. Differences in Kv beta 2 expression between mice and humans may explain the differential K+ conductance increases which accompany T-cell proliferation in these organisms.