KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps

Barro-Soria, René; Rebolledo, Santiago; Liin, Sara I.; Perez, Marta E.; Sampson, Kevin J.; Kass, Robert S.; Larsson, H. Peter

doi:10.1038/ncomms4750

Cited by 88 publications

(167 citation statements)

References 33 publications

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“…On the other hand, as previously reported 34 , WT with KCNE1 showed a large fluorescence change at hyperpolarized potentials far below the threshold of the ionic current ( À 40 mV) and did not saturate either end of the voltage (between À 160 and þ 80 mV). The F-V relationship obviously has two components; the first and leftshifted component relative to G-V curve and the 2nd component activating at depolarized potential and seemingly related to channel opening (G-V relationship) as previously reported by Osteen et al 34 , and as very recently clearly shown by Barro-Soria et al 41 F-V relationships of F232A þ KCNE1 and F279A þ KCNE1 are basically similar to that of WT, having the two fluorescent components. However, the second components are larger in the Phe mutants, especially in F279A þ KCNE1, probably due to the left-shifted G-V curves in the mutants if the second component actually tracks the channel opening as suggested 34 .…”

Section: Resultssupporting

confidence: 80%

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Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening

Nakajo

Kubo

2014

Nat Commun

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In voltage-gated K þ channels, membrane depolarization induces an upward movement of the voltage-sensing domains (VSD) that triggers pore opening. KCNQ1 is a voltage-gated K þ channel and its gating behaviour is substantially modulated by auxiliary subunit KCNE proteins. KCNE1, for example, markedly shifts the voltage dependence of KCNQ1 towards the positive direction and slows down the activation kinetics. Here we identify two phenylalanine residues on KCNQ1, Phe232 on S4 (VSD) and Phe279 on S5 (pore domain) to be responsible for the gating modulation by KCNE1. Phe232 collides with Phe279 during the course of the VSD movement and hinders KCNQ1 channel from opening in the presence of KCNE1. This steric hindrance caused by the bulky amino-acid residues destabilizes the open state and thus shifts the voltage dependence of KCNQ1/KCNE1 channel.

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Section: Resultssupporting

confidence: 80%

“…Therefore, to keep the open state of WT KCNQ1/KCNE1 channel, higher depolarization is required. This final transition from the pre-upstate to the upstate may correspond to the second voltage sensor movement proposed by Barro-Soria 41 , which is seen as the second fluorescent component in Fig. 4a,b.…”

Section: Discussionsupporting

confidence: 57%

Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening

Nakajo

Kubo

2014

Nat Commun

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“…5 A and B) to determine whether the effects of KCNE3-FTL on voltage sensor movement and gate opening resemble the effects of KCNE3 or KCNE1. Similar to the F(V) of KCNQ1/KCNE1 channels (29) (Fig. 5B, dashed red line), the F(V) relation in KCNQ1/KCNE3-FTL channels comprises two components, with a first, major fluorescence component at more negative voltages and a second, minor fluorescence component at more depolarized voltages, in a similar voltage range as gate opening (Fig.…”

Section: Kcne1supporting

confidence: 54%

“…We showed in other studies that KCNE1 shifts a component of the S4 movement of KCNQ1 to more negative voltages relative to that of KCNQ1 alone (although to a lesser extent than KCNE3) (Fig. 1D, red triangles), but shifts the gate opening to more positive voltages (29,30) (Fig. 1D, black triangles).…”

Section: Significancementioning

confidence: 51%

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KCNE1 and KCNE3 Modulate KCNQ1 Channels by Affecting Different Gating Transitions

Barro-Soria

Ramentol

Liin

et al. 2017

Biophysical Journal

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KCNE β-subunits assemble with and modulate the properties of voltage-gated K + channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltagedependent potassium current (I Ks ) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coassembles with KCNQ1 to form K + channels that are voltageindependent K + channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphosphate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-togate coupling.+ (Kv) channels are mainly expressed in excitable cells, where changes in the voltage across the membrane, such as action potentials, demand rapid channel activation and deactivation. Among Kv channels, the KCNQ1 channel (also called Kv7.1 or KvLQT1) differs from most other Kv channels in that KCNQ1 plays key physiological roles in nonexcitable cells, such as in epithelia, in addition to its roles in excitable cells, such as cardiomyocytes. The KCNQ1 channels display dramatically different biophysical properties in various cell types, differences that are thought to be mainly due to the KCNQ1 channel's ability to associate with five tissue-specific KCNE β-subunits to form different K + channel complexes (1-7). KCNQ1 subunits expressed by themselves form voltage-dependent K + channels that open at negative voltages (1, 2) ( Fig. 1 A and D, black squares). However, coassembly of KCNQ1 with KCNE1 (also called MinK) produces a much slower activating potassium current (I Ks ) in the heart that activates at positive voltages ( Fig. 1 B and D, black triangles) and shapes the repolarization phase of cardiac action potentials (1, 2). Mutations in the KCNQ1/KCNE1 complex are linked to life-threatening cardiac arrhythmias, such as torsade de pointes (8, 9). Association of KCNQ1 with KCNE3 (also called MiRP2) produces channels that are voltage-independent in the physiological voltage range (Fig. 1 C and D, black circles) and that are crucial in regulating the transport of water and salt in several epithelial tissues, including the colon, small intestine, and airways (3, 10, 11). Therefore, t...

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Kv7 Channels and Excitability Disorders

Jones

Gamper

Gao

2021

Handbook of Experimental Pharmacology

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KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps

Cited by 88 publications

References 33 publications

Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening

Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening

KCNE1 and KCNE3 Modulate KCNQ1 Channels by Affecting Different Gating Transitions

Kv7 Channels and Excitability Disorders

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