Inactivation of Voltage-Gated Cardiac K+Channels
10.1161/01.res.82.7.739
Crossref journal-article
Ovid Technologies (Wolters Kluwer Health)
Circulation Research (276)
Abstract

Abstract—Inactivation is the process by which an open channel enters a stable nonconducting conformation after a depolarizing change in membrane potential. Inactivation is a widespread property of many different types of voltage-gated ion channels. Recent advances in the molecular biology of K+channels have elucidated two mechanistically distinct types of inactivation, N-type and C-type. N-type inactivation involves occlusion of the intracellular mouth of the pore through binding of a short segment of residues at the extreme N-terminal. In contrast to this “tethered ball” mechanism of N-type inactivation, C-type inactivation involves movement of conserved core domain residues that result in closure of the external mouth of the pore. Although C-type inactivation can show rapid kinetics that approach those observed for N-type inactivation, it is often thought of as a slowly developing and slowly recovering process. Current models of C-type inactivation also suggest that this process involves a relatively localized change in conformation of residues near the external mouth of the permeation pathway. The rate of C-type inactivation and recovery can be strongly influenced by other factors, such as N-type inactivation, drug binding, and changes in [K+]o. These interactions make C-type inactivation an important biophysical process in determining such physiologically important properties as refractoriness and drug binding. C-type inactivation is currently viewed as arising from small-scale rearrangements at the external mouth of the pore. This review will examine the multiplicity of interactions of C-type inactivation with N-terminal–mediated inactivation and drug binding that suggest that our current view of C-type inactivation is incomplete. This review will suggest that C-type inactivation must involve larger-scale movements of transmembrane-spanning domains and that such movements contribute to the diversity of kinetic properties observed for C-type inactivation.

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Rasmusson, R. L., Morales, M. J., Wang, S., Liu, S., Campbell, D. L., Brahmajothi, M. V., & Strauss, H. C. (1998). Inactivation of Voltage-Gated Cardiac K+Channels. Circulation Research, 82(7), 739–750.

Authors 7
  1. Randall L. Rasmusson (first)
  2. Michael J. Morales (additional)
  3. Shimin Wang (additional)
  4. Shuguang Liu (additional)
  5. Donald L. Campbell (additional)
  6. Mulugu V. Brahmajothi (additional)
  7. Harold C. Strauss (additional)
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Dates
Type When
Created 13 years, 2 months ago (June 11, 2012, 8:47 p.m.)
Deposited 4 months, 4 weeks ago (March 30, 2025, 6:15 p.m.)
Indexed 3 months, 3 weeks ago (May 7, 2025, 6:14 a.m.)
Issued 27 years, 4 months ago (April 20, 1998)
Published 27 years, 4 months ago (April 20, 1998)
Published Print 27 years, 4 months ago (April 20, 1998)
Funders 0

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@article{Rasmusson_1998, title={Inactivation of Voltage-Gated Cardiac K+Channels}, volume={82}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.82.7.739}, DOI={10.1161/01.res.82.7.739}, number={7}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Rasmusson, Randall L. and Morales, Michael J. and Wang, Shimin and Liu, Shuguang and Campbell, Donald L. and Brahmajothi, Mulugu V. and Strauss, Harold C.}, year={1998}, month=apr, pages={739–750} }