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J Biol Chem, Vol. 274, Issue 29, 20123-20126, July 16, 1999

The Effects of Shaker -Subunits on the Human Lymphocyte K⁺ Channel Kv1.3

Tom McCormack, Ken McCormack^¶, Marcela S. Nadal, Eric Vieira, Ander Ozaita, and Bernardo Rudy

From the Departments of  Physiology and Neuroscience and of  Pathology, New York University, School of Medicine, New York, New York 10016 and ^¶ Ventana Genetics, Salt Lake City, Utah 84108

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 post-transcriptional regulation. In other tissues Shaker K⁺ channel proteins physically associate with cytoplasmic -subunits (Kv1-3). Recently it has been shown that Kv1 and Kv2 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 subunits substantially increase K⁺ current amplitudes when coexpressed with their Kv1.3 counterpart, and that unlike in mouse, protein levels of human Kv2 remain constant upon activation. Differences in Kv2 expression between mice and humans may explain the differential K⁺ conductance increases which accompany T-cell proliferation in these organisms.

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