MODES OF REGULATION OF SHAB K+ CHANNEL ACTIVITY BY THE KV8.1 SUBUNIT

The Rv8.1 subunit is unable to generate K+ channel activity in Xenopus oocytes or in COSm6 cells. The Kv8.1 subunit expressed at high levels acts as a specific suppressor of the activity of Kv2 and Kv3 channels in Xenopus oocytes (Hugnot, J. P., Salinas, M., Lesage, F., Guillemar e, E., Weille, J., Heurteaux, C., Mattei, M. G., and Lazdunski, M. (19 96) EMBO J. 15, 3322-3331). At lower levels, Kv8.1 associates with Kv2 .1 and Kv2.2 to form hybrid Kv8.1/Kv2 channels, which have new biophys ical properties and more particularly modified properties of the inact ivation process as compared with homopolymers of Kv2.1 or Kv2.2 channe ls. The same effects have been seen by coexpressing the Kv8.1 subunit and the Kv2.2 subunit in COSm6 cells. In these cells, Kv8.1 expressed alone remains in intracellular compartments, but it can reach the plas ma membrane when it associates with Kv2.2, and it then also forms new types of Kv8.1/Kv2.2 channels. Present results indicate that Kv8.1 whe n expressed at low concentrations acts as a modifier of Kv2.1 and Kv2. 2 activity, while when expressed at high concentrations in oocytes it completely abolishes Kv2.1, Kv2.2, or Kv3.4 K+ channel activity. The S 6 segment of Kv8.1 is atypical and contains the structural elements th at modify inactivation of Kv2 channels.