Gating charge differences between two voltagegated K+ channels are due to the specific charge content of their respective S4 regions

Logothetis, Diomedes E.; Kammen, Bamidele F.; Lindpaintner, Klaus; Bisbas, Drosos S; Nadal‐Ginard, Bernardo

doi:10.1016/0896-6273(93)90060-5

Cited by 51 publications

(49 citation statements)

References 31 publications

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“…Other estimates of the gating charge from limiting slope experiments have been reported apart from those presented in Table 1 44 These last ones are probably in error due to voltage control problems in TEVC as well as the open probability not being low enough.…”

Section: Magnitude Of the Charge Movementmentioning

confidence: 99%

“…43,44 Experimentally this contribution has been demonstrated for only a handful of ion channels. [45][46][47] As the transmembrane voltage changes polarity during a depolarization and the cytoplasmic side becomes positive, the energy on the S4 charges changes and thus the whole S4 undergoes movement, which is directed in the outward direction.…”

Section: Molecular Mechanism Of Voltage Sensingmentioning

confidence: 99%

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Functional diversity of potassium channel voltage-sensing domains

Islas¹

2016

Channels

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Voltage-gated potassium channels or Kv's are membrane proteins with fundamental physiological roles. They are composed of 2 main functional protein domains, the pore domain, which regulates ion permeation, and the voltage-sensing domain, which is in charge of sensing voltage and undergoing a conformational change that is later transduced into pore opening. The voltagesensing domain or VSD is a highly conserved structural motif found in all voltage-gated ion channels and can also exist as an independent feature, giving rise to voltage sensitive enzymes and also sustaining proton fluxes in proton-permeable channels. In spite of the structural conservation of VSDs in potassium channels, there are several differences in the details of VSD function found across variants of Kvs. These differences are mainly reflected in variations in the electrostatic energy needed to open different potassium channels. In turn, the differences in detailed VSD functioning among voltage-gated potassium channels might have physiological consequences that have not been explored and which might reflect evolutionary adaptations to the different roles played by Kv channels in cell physiology.

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Section: Magnitude Of the Charge Movementmentioning

confidence: 99%

Section: Molecular Mechanism Of Voltage Sensingmentioning

confidence: 99%

Functional diversity of potassium channel voltage-sensing domains

Islas¹

2016

Channels

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“…Channel properties were tested in Xenopus oocytes injected with in vitro transcribed cRNA (50 ng/oocyte) using the 2-microelectrode voltage-clamp technique as previously described. 19 Single ventricular myocytes were isolated either from the entire left ventricle or separately from the left ventricular apex and septum, and whole-cell voltage-and current-clamp studies were performed at room temperature or 35°C using a Dagan 3900A (Dagan Corporation) or an Axopatch-1D (Axon Instruments) patch-clamp amplifier interfaced to a microcomputer equipped with a Digidata 1200 Series analog-to-digital interface and pClamp 7 software (Axon Instruments). 9,20 Membrane capacitance and series resistance were compensated electronically (Ͼ85%).…”

Section: Electrophysiologymentioning

confidence: 99%

Targeted Replacement of Kv1.5 in the Mouse Leads to Loss of the 4-Aminopyridine–Sensitive Component of I _K,slow and Resistance to Drug-Induced QT Prolongation

London

Guo

Xiang

et al. 2001

Circulation Research

103

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Abstract-The K ϩ channel mKv1.5 is thought to encode a 4-aminopyridine (4-AP)-sensitive component of the current I K,slow in the mouse heart. We used gene targeting to replace mKv1.5 with the 4-AP-insensitive channel rKv1.1 (SWAP mice) and directly test the role of Kv1.5 in the mouse ventricle. Kv1.5 RNA and protein were undetectable, rKv1.1 was expressed, and Kv2.1 protein was upregulated in homozygous SWAP hearts. The density of the K ϩ current I K,slow (depolarizations to ϩ40 mV, pA/pF) was similar in left ventricular myocytes isolated from SWAP homozygotes (17Ϯ1, nϭ27) and littermate controls (16Ϯ2, nϭ19). The densities and properties of I peak , I to,f , I to,s , and I ss were also unchanged. In homozygous SWAP myocytes, the 50-mol/L 4-AP-sensitive component of I K,slow was absent (nϭ6), the density of the 20-mmol/L tetraethylammonium-sensitive component of I K,slow was increased (9Ϯ1 versus 5Ϯ1, PϽ0.05), and no 100-to 200-nmol/L ␣-dendrotoxin-sensitive current was found (nϭ8). APD 90 in SWAP myocytes was similar to controls at baseline but did not prolong in response to 30 mol/L 4-AP. Similarly, QTc (ms) was not prolonged in anesthetized SWAP mice (64Ϯ2, homozygotes, nϭ9; 62Ϯ2, controls, nϭ9), and injection with 4-AP prolonged QTc only in controls (63Ϯ1, homozygotes; 72Ϯ2, controls; PϽ0.05). SWAP mice had no increase in arrhythmias during ambulatory telemetry monitoring. Thus, Kv1.5 encodes the 4-AP-sensitive component of I K,slow in the mouse ventricle and confers sensitivity to 4-AP-induced prolongation of APD and QTc. Compensatory upregulation of Kv2.1 may explain the phenotypic differences between SWAP mice and the previously described transgenic mice expressing a truncated dominant-negative Kv1.

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“…Further support indicating that S4 is involved in voltage sensing comes from experiments in which S4 domains are swapped. In these situations the voltage-dependence is conferred largely by the substituted S4 domain [13,14].…”

Section: Introductionmentioning

confidence: 99%

The conformational analysis of a synthetic S4 peptide corresponding to a voltage‐gated potassium ion channel protein

et al. 1994

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The S4 region of the Drosophila Shaker voltage-gated K' channel has been proposed to function as a voltage-sensor. We have synthesised a peptide corresponding to this S4 region. Structural studies on the S4 peptide were conducted using Fourier transform infrared (FTIR) spectroscopy. Spectra were obtained for the peptide dissolved in aqueous solution, in trifluoroethanol solvent and also after reconstitution into lipid bilayers and micelles. The peptide in trifluoroethanol adopts an a-helical conformation which is in good agreement with the results of a recent 2D NMR study on the structure of a S4 peptide corresponding to the rat brain sodium channel [(1989) FEBS Lett. 257, 113-l 171. A predominantly a-helical structure is also observed when the S4 peptide is present in aqueous lysophosphatidylcholine micelles, in dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol lipid bilayers. In contrast to this, the S4 peptide in aqueous solution is in a random coil conformation. The coil-to-helix transition observed for the S4 peptide upon its transfer from aqueous solution to lipid membrane indicates that it has a high degree of conformational flexibility and can undergo large changes in its structure in response to its environment. This may have important implications for its role in the voltage activation process during which the S4 peptide has been postulated to, at least partially, move from a lipid bilayer to an aqueous extracellular media [(1992) Biophys J. 62, 238-2501. The results of our study lend support to such a model.

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Gating charge differences between two voltagegated K+ channels are due to the specific charge content of their respective S4 regions

Cited by 51 publications

References 31 publications

Functional diversity of potassium channel voltage-sensing domains

Functional diversity of potassium channel voltage-sensing domains

Targeted Replacement of Kv1.5 in the Mouse Leads to Loss of the 4-Aminopyridine–Sensitive Component of I _K,slow and Resistance to Drug-Induced QT Prolongation

The conformational analysis of a synthetic S4 peptide corresponding to a voltage‐gated potassium ion channel protein

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Gating charge differences between two voltagegated K+ channels are due to the specific charge content of their respective S4 regions

Cited by 51 publications

References 31 publications

Functional diversity of potassium channel voltage-sensing domains

Functional diversity of potassium channel voltage-sensing domains

Targeted Replacement of Kv1.5 in the Mouse Leads to Loss of the 4-Aminopyridine–Sensitive Component of I K,slow and Resistance to Drug-Induced QT Prolongation

The conformational analysis of a synthetic S4 peptide corresponding to a voltage‐gated potassium ion channel protein

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Targeted Replacement of Kv1.5 in the Mouse Leads to Loss of the 4-Aminopyridine–Sensitive Component of I _K,slow and Resistance to Drug-Induced QT Prolongation