Probing the Transition State of the Allosteric Pathway of the Shaker Kv Channel Pore by Linear Free-Energy Relations

Azaria, Reshef; Orr, Irit; Ben-Abu, Yuval; Yifrach, Ofer

doi:10.1016/j.jmb.2010.08.041

Cited by 9 publications

(9 citation statements)

References 33 publications

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“…We recognize that experimental elucidation of the coupling pathway may prove to be difficult. One possible approach has been suggested by Yifrach and colleagues (Sadovsky and Yifrach, 2007; Azaria et al, 2010), which focuses on revealing the nature of the transition state separating two kinetically distinguishable states. Required isolation of one transition out of the known numerous states in K V channels (Zagotta et al, 1994; Schoppa and Sigworth, 1998) will be undoubtedly challenging.…”

Section: Coupling Of Activation and C-type Inactivationmentioning

confidence: 99%

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

Hoshi

Armstrong

2013

Journal of General Physiology

138

183

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Section: Coupling Of Activation and C-type Inactivationmentioning

confidence: 99%

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

Hoshi

Armstrong

2013

Journal of General Physiology

138

183

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“…Coupling between the K-channel activation gate at the bundle-crossing of inner helices and the selectivity filter gate has been proposed for KcsA (19)(20)(21) and Kv channels (22)(23)(24). However, the allosteric mechanism of this coupling (which can also be bidirectional) is only beginning to be defined.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Kir1.1 Inactivation by Extracellular Ca and Mg

Sackin

Nanazashvili

et al. 2011

Biophysical Journal

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Kir1.1 inactivation, associated with transient internal acidification, is strongly dependent on external K, Ca, and Mg. Here, we show that in 1 mM K, a 15 min internal acidification (pH 6.3) followed by a 30 min recovery (pH 8.0) produced 84 ± 3% inactivation in 2 mM Ca but only 18 ± 4% inactivation in the absence of external Ca and Mg. In 100 mM external K, the same acidification protocol produced 29 ± 4% inactivation in 10 mM external Ca but no inactivation when extracellular Ca was reduced below 2 mM (with 0 Mg). However, chelation of external K with 15 mM of 18-Crown-6 (a crown ether) restored inactivation even in the absence of external divalents. External Ca was more effective than external Mg at producing inactivation, but Mg caused a greater degree of open channel block than Ca, making it unlikely that Kir1.1 inactivation arises from divalent block per se. Because the Ca sensitivity of inactivation persisted in 100 mM external K, it is also unlikely that Ca enhanced Kir1.1 inactivation by reducing the local K concentration at the outer mouth of the channel. The removal of four surface, negative side chains at E92, D97, E104, and E132 (Kir1.1b) increased the sensitivity of inactivation to external Ca (and Mg), whereas addition of a negative surface charge (N105E-Kir1.1b) decreased the sensitivity of inactivation to Ca and Mg. This result is consistent with the notion that negative surface charges stabilize external K in the selectivity filter or at the S(0)-K binding site just outside the filter. Extracellular Ca and Mg probably potentiate the slow, K-dependent inactivation of Kir1.1 by decreasing the affinity of the channel for external K independently of divalent block. The removal of external Ca and Mg largely eliminated both Kir1.1 inactivation and the K-dependence of pH gating, thereby uncoupling the selectivity filter gate from the cytoplasmic-side bundle-crossing gate.

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“…Energetic interactions between residues and associated conformational rearrangements along a structural path between the inner and outer pore may underlie their coupling101112 and has been proposed to explain a set of high resolution crystal structures obtained from the potassium channel KcsA, from Streptomyces lividans 13. KcsA is gated mainly by protons, rather than by voltage, but the proton-activated currents decay over time in a manner that is similar to C-type inactivation in Kv channels.…”

mentioning

confidence: 99%

Allosteric coupling of the inner activation gate to the outer pore of a potassium channel

Peters¹,

Fedida

Accili³

2013

Sci Rep

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In potassium channels, functional coupling of the inner and outer pore gates may result from energetic interactions between residues and conformational rearrangements that occur along a structural path between them. Here, we show that conservative mutations of a residue near the inner activation gate of the Shaker potassium channel (I470) modify the rate of C-type inactivation at the outer pore, pointing to this residue as part of a pathway that couples inner gate opening to changes in outer pore structure and reduction of ion flow. Because they remain equally sensitive to rises in extracellular potassium, altered inactivation rates of the mutant channels are not secondary to modified binding of potassium to the outer pore. Conservative mutations of I470 also influence the interaction of the Shaker N-terminus with the inner gate, which separately affects the outer pore.

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Probing the Transition State of the Allosteric Pathway of the Shaker Kv Channel Pore by Linear Free-Energy Relations

Cited by 9 publications

References 33 publications

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

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

Modulation of Kir1.1 Inactivation by Extracellular Ca and Mg

Allosteric coupling of the inner activation gate to the outer pore of a potassium channel

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