Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Feb;141(2):151-60.
doi: 10.1085/jgp.201210888. Epub 2013 Jan 14.

C-type inactivation of voltage-gated K+ channels: pore constriction or dilation?

Toshinori Hoshi  1 , Clay M Armstrong
Affiliations

C-type inactivation of voltage-gated K+ channels: pore constriction or dilation?

Toshinori Hoshi et al. J Gen Physiol. 2013 Feb.
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Postulated occupancy states of the selectivity filter, shown in a section through the pore. (A) Conducting states. Two K+ ions complexed with carbonyl oxygens are thought to be in the filter at any instant, in sites 2 and 4, or sites 1 and 3. Occupancy of sites 2 and 4 is more probable at resting Vm. When the gate opens, IK is normally outward, and occupancy oscillates between sites 4,2 and 3,1. This oscillation is driven by voltage, and outward movement of the ion shown in the vestibule, which sheds its watery coat and enters site 4. The ion in site 1 is driven to the site shown just external to the filter as it rehydrates. The numbering of the amino acid residues in the filter in and just above the filter of 2R9R (left) and ShB (right) are shown. (B) Postulate of a C-type inactivated channel: the outermost site 1 of the selectivity filter dilates and cannot effectively complex a K+ ion, and thus cannot accept an ion moving outward from site 2. A hydrated Na+ ion may be present in site 1, as shown. (C) Dilated state in the complete absence of K+ ions. The selectivity filter dilates from top to bottom when close-fitting K+ ions are not present and the carbonyl oxygens of the filter mutually repel. This allows partially hydrated Na+ and other large cations to permeate. (D) Defunct state. The selectivity filter is hopelessly denatured by carbonyl–carbonyl repulsion. Ion permeation is not possible. Structural details of the defunct state are unknown.
Figure 2.
Figure 2.
Structural arrangements of the Kv1.2-2.1 chimera (2R9R) near the pore. (A) The outermost K+ ion in site 1 (S1) of the filter is tightly complexed to the four carbonyls of Y373 (Y445) (Y) and the four carbonyls of G372 (G444) (G), just below. Several residues important in C-type inactivation are labeled. The carbon atoms of these residues are rendered with different colors for clarity: gray, G372 (Y444) in ShB; cyan, Y373 (Y445); orange, D375 (D447); yellow, V377 (T449); green, W362 (W434). Y373 (Y445) and G372 (G444) from all four subunits are shown, but only one set of D375 (D447), W362 (W434), and V377 (T449) is shown as spheres. D375/447 and W362/434 residues shown are from one subunit, whereas V377 (T449) is from an adjacent subunit. The circles mark three of the close contacts postulated to be important for C-type inactivation (see text). Prepared using MacPyMol (version 0.99). (B) A “temperature” map of a section obtained from the B-factor values along the pore axis of 2R9R. Dark blue marks regions of high stability, ranging through light blue, yellow, orange, and red as stability decreases progressively away from the selectivity filter. Prepared using RasMol.
Figure 3.
Figure 3.
An expanded view of the outer mouth of the selectivity filter of the Kv1.2-2.1 chimera and two simulated mutations. The four outermost Y373 carbonyl oxygens outline the pore, but only one tyrosine is shown in full. (A) The conducting conformation of the filter mouth, taken from the Kv1.2-2.1 chimera. Y373 (Y445) has close contacts with W362 (W434) and V377 (T449). (B) A simulated mutation of the Kv1.2-2.1 chimera that replaces V377 (T449) with V377A (T449A), allowing Y373 (Y445) to rotate and dilate the filter mouth. The mutation in effect deletes the two γ carbons of V377 (T449), removing a contact that locks Y373 (Y445) in the conducting, nondilated position. (C) Simulated mutation W362 (W434) of the Kv1.2-2.1 chimera that replaces W362 (W434) with F362 (F434). Relative to W362 (W434), F362 (F434) is rotated clockwise in this view; it presses against the ring of Y373 (Y445), causing Y373 (Y445) to rotate counterclockwise, dilating the filter mouth. The angle of view is the same throughout the figure. The images were prepared using MacPyMol (version 0.99).
Figure 4.
Figure 4.
“Four-legged runner” model of the coupling of S4 activation and C-type inactivation. A Kv1.2-2.1 chimera (2R9R) is viewed from the extracellular side. Consistent with the literature, a conformational wave begins with contact between F344 in TMS5 and R293 in TMS4, when the latter is driven outward by voltage. The wave spreads through the illustrated residues to the region of the pore mouth, causing, in susceptible mutants, dilation of the pore mouth and C-type inactivation. The Kv1.2-2.1 chimera does not undergo C-type inactivation because V377 locks Y373 in position; the pore mouth here is not dilated. All of the residues presented as spheres have been shown to affect C-type inactivation. The carbon atoms of these residues are shown using different colors for clarity. TMS1–TMS4 identify the respective transmembrane segments. Prepared using MacPyMol (version 0.99).
See this image and copyright information in PMC

References

    1. Adelman J.P., Bond C.T., Pessia M., Maylie J. 1995. Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron. 15:1449–1454 10.1016/0896-6273(95)90022-5 - DOI - PubMed
    1. Aldrich R.W., Jr, Getting P.A., Thompson S.H. 1979. Mechanism of frequency-dependent broadening of molluscan neurone soma spikes. J. Physiol. 291:531–544 - PMC - PubMed
    1. Almers W., Armstrong C.M. 1980. Survival of K+ permeability and gating currents in squid axons perfused with K+-free media. J. Gen. Physiol. 75:61–78 10.1085/jgp.75.1.61 - DOI - PMC - PubMed
    1. Azaria R., Irit O., Ben-Abu Y., Yifrach O. 2010. Probing the transition state of the allosteric pathway of the Shaker Kv channel pore by linear free-energy relations. J. Mol. Biol. 403:167–173 10.1016/j.jmb.2010.08.041 - DOI - PubMed
    1. Baukrowitz T., Yellen G. 1995. Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms. Neuron. 15:951–960 10.1016/0896-6273(95)90185-X - DOI - PubMed

Publication types

MeSH terms

Substances