Abstract
The "ball and chain" model has been shown to be suitable for explaining the rapid inactivation of voltage-dependent K+ channels. For the Drosophila Shaker K+ channel (ShB), the first 20 residues of the amino terminus have been identified as the inactivation ball that binds to the open channel pore and blocks ion flow (Hoshi, T., Zagotta, W. N., and 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 structural elements responsible for rapid inactivation of a mammalian transient type K+ channel (rat Kv1.4) by constructing various mutants in the amino terminus and expressing them in Xenopus oocytes. Although it has been reported that the initial 37 residues might form the inactivation 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 that not only the initial 37 residues, but also the following region, residues 40-68, could function independently as an inactivation gate. Like the Shaker inactivation ball, both potential inactivation domains have a hydrophobic amino-terminal region and a hydrophilic carboxyl-terminal region having net positive charge, which is essential for the domains to function as an inactivation gate.
Highlights
Aldrich and co-workers have shown that a “ball and chain” model, originally proposed for Na1 channel inactivation [4], can explain the rapid inactivation of a Drosophila Shaker K1 channel [1, 2]
In mammalian transient type K1 channels, the ball and chain structure had not been well defined, it had been shown that deletion of various lengths from the amino-terminal region of Kv1.4 disrupted rapid inactivation suggesting the presence of a “ball” structure [6, 7]
The inactivation of D2–28 seems to be qualitatively different from that of Kv1.4. Since it has been shown for Shaker K1 channel and RHK1 that elevating [K1]o can accelerate the recovery rate [11, 12], we investigated the effects of changing [K1]o on the recovery rate
Summary
Aldrich and co-workers have shown that a “ball and chain” model, originally proposed for Na1 channel inactivation [4], can explain the rapid inactivation of a Drosophila Shaker K1 channel [1, 2]. D2–39 & D69 –162, with only the second potential inactivation ball, showed more rapid inactivation than Kv1.4 (Fig. 3B, upper panel). Effects of Deleting Positive Charges—Since both potential inactivation balls contain net positive charge in the carboxyl termini, we constructed mutants in which some positive charges were removed to examine the contribution of charge to rapid inactivation.
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