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Biophys J
2009 Aug 19;974:1058-66. doi: 10.1016/j.bpj.2009.05.056.
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An intersubunit salt bridge near the selectivity filter stabilizes the active state of Kir1.1.
Sackin H
,
Nanazashvili M
,
Li H
,
Palmer LG
,
Walters DE
.
???displayArticle.abstract??? ROMK (Kir1.1) potassium channels are closed by internal acidification with a pKa of 6.7 +/- 0.01 in 100 mM external K and a pKa of 7.0 +/- 0.01 in 1 mM external K. Internal acidification in 1 mM K (but not 100 mM K) not only closed the pH gate but also inactivated Kir1.1, such that realkalization did not restore channel activity until high K was returned to the bath. We identified a new putative intersubunit salt bridge (R128-E132-Kir1.1b) in the P-loop of the channel near the selectivity filter that affected the K sensitivity of the inactivation process. Mutation of either R128-Kir1.1b or E132-Kir1.1b caused inactivation in both 1 mM and 100 mM external K during oocyte acidification. However, 300 mM external K (but not 200 mM Na + 100 mM K) protected both E132Q and R128Y from inactivation. External application of a modified honey-bee toxin, tertiapin Q (TPNQ), also protected Kir1.1 from inactivation in 1 mM K and protected E132Q and R128Y from inactivation in 100 mM K, which suggests that TPNQ binding to the outer mouth of the channel stabilizes the active state. Pretreatment of Kir1.1 with external Ba prevented Kir1.1 inactivation, similar to pretreatment with TPNQ. In addition, mutations that disrupted transmembrane helix H-bonding (K61M-Kir1.1b) or stabilized a selectivity filter to helix-pore linkage (V121T-Kir1.1b) also protected both E132Q and R128Y from inactivation in 1 mM K and 100 mM K. Our results are consistent with Kir inactivation arising from conformational changes near the selectivity filter, analogous to C-type inactivation.
Armstrong,
Ionic pores, gates, and gating currents.
1974, Pubmed
Armstrong,
Ionic pores, gates, and gating currents.
1974,
Pubmed
Baukrowitz,
Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel.
1996,
Pubmed
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Choe,
A conserved cytoplasmic region of ROMK modulates pH sensitivity, conductance, and gating.
1997,
Pubmed
,
Xenbase
Choi,
Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.
1991,
Pubmed
Cordero-Morales,
Molecular driving forces determining potassium channel slow inactivation.
2007,
Pubmed
,
Xenbase
Cordero-Morales,
Voltage-dependent gating at the KcsA selectivity filter.
2006,
Pubmed
Cordero-Morales,
Molecular determinants of gating at the potassium-channel selectivity filter.
2006,
Pubmed
Dahlmann,
Regulation of Kir channels by intracellular pH and extracellular K(+): mechanisms of coupling.
2004,
Pubmed
,
Xenbase
Dibb,
Molecular basis of ion selectivity, block, and rectification of the inward rectifier Kir3.1/Kir3.4 K(+) channel.
2003,
Pubmed
Doi,
Extracellular K+ and intracellular pH allosterically regulate renal Kir1.1 channels.
1996,
Pubmed
,
Xenbase
Flynn,
Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels.
2001,
Pubmed
,
Xenbase
Gómez-Lagunas,
Shaker B K+ conductance in Na+ solutions lacking K+ ions: a remarkably stable non-conducting state produced by membrane depolarizations.
1997,
Pubmed
Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase
Jiang,
The barium site in a potassium channel by x-ray crystallography.
2000,
Pubmed
Jin,
Mechanisms of inward-rectifier K+ channel inhibition by tertiapin-Q.
1999,
Pubmed
,
Xenbase
Jin,
A novel high-affinity inhibitor for inward-rectifier K+ channels.
1998,
Pubmed
,
Xenbase
Jin,
Synthesis of a stable form of tertiapin: a high-affinity inhibitor for inward-rectifier K+ channels.
1999,
Pubmed
,
Xenbase
Kiss,
Contribution of the selectivity filter to inactivation in potassium channels.
1999,
Pubmed
Kuo,
Crystal structure of the potassium channel KirBac1.1 in the closed state.
2003,
Pubmed
Kurata,
A structural interpretation of voltage-gated potassium channel inactivation.
2006,
Pubmed
Lange,
Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR.
2006,
Pubmed
,
Xenbase
Larsson,
A conserved glutamate is important for slow inactivation in K+ channels.
2000,
Pubmed
,
Xenbase
Leipziger,
PKA site mutations of ROMK2 channels shift the pH dependence to more alkaline values.
2000,
Pubmed
,
Xenbase
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
Loboda,
Dilated and defunct K channels in the absence of K+.
2001,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
MacKerell,
All-atom empirical potential for molecular modeling and dynamics studies of proteins.
1998,
Pubmed
Molina,
Pore mutations in Shaker K+ channels distinguish between the sites of tetraethylammonium blockade and C-type inactivation.
1997,
Pubmed
Molina,
Pore mutations alter closing and opening kinetics in Shaker K+ channels.
1998,
Pubmed
Phillips,
Gating dependence of inner pore access in inward rectifier K(+) channels.
2003,
Pubmed
Ramu,
Titration of tertiapin-Q inhibition of ROMK1 channels by extracellular protons.
2001,
Pubmed
,
Xenbase
Rapedius,
H bonding at the helix-bundle crossing controls gating in Kir potassium channels.
2007,
Pubmed
,
Xenbase
Rapedius,
Structural and functional analysis of the putative pH sensor in the Kir1.1 (ROMK) potassium channel.
2006,
Pubmed
,
Xenbase
Rasmusson,
Inactivation of voltage-gated cardiac K+ channels.
1998,
Pubmed
Sackin,
Regulation of ROMK by extracellular cations.
2001,
Pubmed
,
Xenbase
Sackin,
Role of conserved glycines in pH gating of Kir1.1 (ROMK).
2006,
Pubmed
,
Xenbase
Sackin,
Structural locus of the pH gate in the Kir1.1 inward rectifier channel.
2005,
Pubmed
,
Xenbase
Sackin,
Permeant cations and blockers modulate pH gating of ROMK channels.
2003,
Pubmed
,
Xenbase
Sackin,
External K activation of Kir1.1 depends on the pH gate.
2007,
Pubmed
Sadja,
Coupling Gbetagamma-dependent activation to channel opening via pore elements in inwardly rectifying potassium channels.
2001,
Pubmed
,
Xenbase
Schulte,
pH-dependent gating of ROMK (Kir1.1) channels involves conformational changes in both N and C termini.
1998,
Pubmed
,
Xenbase
Schulte,
K(+)-dependent gating of K(ir)1.1 channels is linked to pH gating through a conformational change in the pore.
2001,
Pubmed
,
Xenbase
Shieh,
Mechanisms for the time-dependent decay of inward currents through cloned Kir2.1 channels expressed in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Swenson,
K+ channels close more slowly in the presence of external K+ and Rb+.
1981,
Pubmed
Xiao,
Localization of PIP2 activation gate in inward rectifier K+ channels.
2003,
Pubmed
,
Xenbase
Yang,
Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel.
1997,
Pubmed
,
Xenbase
Yellen,
The moving parts of voltage-gated ion channels.
1998,
Pubmed
Zachariae,
The molecular mechanism of toxin-induced conformational changes in a potassium channel: relation to C-type inactivation.
2008,
Pubmed
,
Xenbase
Zhang,
Localization of the pH gate in Kir1.1 channels.
2006,
Pubmed
,
Xenbase
Zhou,
Mutations in the pore region of ROMK enhance Ba2+ block.
1996,
Pubmed
,
Xenbase
