%0 Journal Article %1 Rasm_1998_739 %A Rasmusson, R. L. %A Morales, M. J. %A Wang, S. %A Liu, S. %A Campbell, D. L. %A Brahmajothi, M. V. %A Strauss, H. C. %D 1998 %J Circ. Res. %K 9562433 Allosteric Animals, Binding, Channel Channels, Fr, Gating, Heart, Humans, Ion Membrane Peptide Potassium Potentials, Protein Regulation, agments, %N 7 %P 739--750 %T Inactivation of voltage-gated cardiac K$^+$ channels. %V 82 %X 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.

@article{Rasm_1998_739, 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.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Rasmusson, R. L. and Morales, M. J. and Wang, S. and Liu, S. and Campbell, D. L. and Brahmajothi, M. V. and Strauss, H. C.}, biburl = {https://www.bibsonomy.org/bibtex/21ca04de37703d942b2638136df4eb00e/hake}, description = {The whole bibliography file I use.}, file = {Rasm_1998_739.pdf:Rasm_1998_739.pdf:PDF}, interhash = {cae9aa5e25ef8d0fa4871c596264bfd6}, intrahash = {1ca04de37703d942b2638136df4eb00e}, journal = {Circ. Res.}, keywords = {9562433 Allosteric Animals, Binding, Channel Channels, Fr, Gating, Heart, Humans, Ion Membrane Peptide Potassium Potentials, Protein Regulation, agments,}, month = Apr, number = 7, pages = {739--750}, pmid = {9562433}, timestamp = {2009-06-03T11:21:26.000+0200}, title = {Inactivation of voltage-gated cardiac {K}$^{+}$ channels.}, volume = 82, year = 1998 }