A MAMMALIAN TRANSIENT TYPE K+ CHANNEL, RAT KV1.4, HAS 2 POTENTIAL DOMAINS THAT COULD PRODUCE RAPID INACTIVATION

The ''ball and chain'' model has been shown to be suitable for explain ing the rapid inactivation of voltage-dependent K+ channels, For the D rosophila Shaker K+ channel (ShB), the first 20 residues of the amino terminus have been identified as the inactivation ball that binds to t he open channel pore and blocks ion flow (Hoshi, T., Zagotta, W. N., a nd Aldrich, R. W. (1990) Science 250, 533-538; Zagotta, W. N., Hoshi, T., and Aldrich, R. W. (1990) Science 250, 568-571), We studied the st ructural elements responsible for rapid inactivation of a mammalian tr ansient type K+ channel (rat Kv1.4) by constructing various mutants in the amino terminus and expressing them in Xenopus oocytes, Although i t has been reported that the initial 37 residues might form the inacti vation ball for rat Kv1.4 (Tseng-Crank, J., Yao, J.-A., Berman M. F., and Tseng, G.-N. (1993) J. Gen. Physiol, 102, 1057-1083), we found tha t not only the initial 37 residues, but also the following region, res idues 40-68, could function independently as an inactivation gate, Lik e the Shaker inactivation ball, both potential inactivation domains ha ve a hydrophobic amino-terminal region and a hydrophilic carboxyl-term inal region having net positive charge, which is essential for the dom ains to function as an inactivation gate.