FUNCTION AND ASSEMBLY OF K+ CHANNELS IN T LYMPHOCYTES

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This research program proposes to study the biophysical properties and subunit interactions of voltage-gated K+ channels and their role in the physiology of T lymphocytes. This proposal is divided into three main projects. The first project determines the impact of K+ channel gating, inactivation kinetics and cumulative inactivation on membrane potential, regulatory volume decrease, and apoptosis. Wile-type and mutated K+ channels will be heterologously expressed in a mouse T cell line, CTLL-2, which lacks endogenous K+ channels. The second project determines turnover rates of functional K+ channel isoforms, and the physiological impact of irreversible ablation of K+ channels in primary human T lymphocytes. This will entail use of a new technique, chromophore-assisted laser inactivation. The third project evaluates specific models of assembly and suppression of T cell voltage-gated K+ channels, specifically, Kv1.3, in cell-free ad in vitro cellular expression systems. This will entail expression of wild-type and truncated K+ channel DNA sequences.