N-type Inactivation in the Mammalian Shaker K+ Channel Kv1.4 |
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Authors: | TE Lee LH Philipson DJ Nelson |
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Institution: | (1) Department of Neurology, The University of Chicago, Chicago, IL 60637, US;(2) Department of Medicine, The University of Chicago, Chicago, IL 60637, US;(3) Department of Pharmacological and Physiological Sciences, The University of Chicago, Chicago, IL 60637, US |
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Abstract: | Mammalian voltage-gated K+ channels are oligomeric proteins, some of which may be composed in vivo of subunits derived from several similar genes. We
have studied N-type inactivation in the rapidly inactivating Kv1.4 channel and, in specific, heteromultimers of this gene
product with Kv1.5 noninactivating subunits. Heteromultimeric channels were analyzed for the stoichiometry of Kv1.4:Kv1.5
subunits by observing shifts in the midpoints of steady-state availability from that of homomultimeric channels. This analysis
was employed to examine inactivation of heteromultimeric channels expressed in Xenopus oocytes using two model systems: by expression of a Kv1.4–Kv1.5 tandem fusion construct and by coexpression of native Kv1.4
and Kv1.5 channels across a wide relative concentration range of microinjected mRNA. Additionally, inactivation was examined
in coexpression experiments of N-terminal deletion mutants of Kv1.4. We found that (i) a single inactivating subunit conferred
inactivation in all hetero-multimers studied; (ii) the rate of inactivation could not be distinguished in channels containing
two inactivating subunits from those containing one inactivating subunit; and (iii) large deletions in the linker region between
the N-terminal inactivation region and the first membrane-spanning domain had no effect on the rate of inactivation. These
data confirm the importance of the proximal N-terminal region in the inactivation of mammalian Kv1.4 channels, and suggest
that the inactivation particle remains in close proximity to the permeation pathway even when the channel is in the open state.
Received: 24 August 1995/Revised: 7 February 1996 |
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Keywords: | :Xenopus oocyte — Voltage clamp — Mutagenesis — Heteromultimers — Ion channels |
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