scholarly journals Intramolecular interactions that control voltage sensitivity in the jShak1 potassium channel fromPolyorchis penicillatus

2016 ◽  
Vol 220 (3) ◽  
pp. 469-477
Author(s):  
Nazlee Sharmin ◽  
Warren J. Gallin
Keyword(s):  
Potassium Channel ◽  
Intramolecular Interactions ◽  
Control Voltage ◽  
Voltage Sensitivity

scholarly journals Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels

2016 ◽  
Vol 147 (6) ◽  
pp. 437-449 ◽  
Author(s):  
Petronel Tuluc ◽  
Bruno Benedetti ◽  
Pierre Coste de Bagneaux ◽  
Manfred Grabner ◽  
Bernhard E. Flucher
Keyword(s):  
Calcium Channels ◽  
Molecular Mechanisms ◽  
Voltage Dependence ◽  
Specific Interaction ◽  
Site Directed Mutagenesis ◽  
Control Voltage ◽  
Voltage Sensitivity ◽  
Voltage Sensing ◽  
Activation Kinetics ◽  
Transmembrane Segments

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3–S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3–S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3–S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3–S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3–S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms within the IV and I VSDs, respectively.

scholarly journals A Theoretical Model for Calculating Voltage Sensitivity of Ion Channels and the Application on Kv1.2 Potassium Channel

2012 ◽  
Vol 102 (8) ◽  
pp. 1815-1825 ◽  
Author(s):  
Huaiyu Yang ◽  
Zhaobing Gao ◽  
Ping Li ◽  
Kunqian Yu ◽  
Ye Yu ◽  
...  
Keyword(s):  
Theoretical Model ◽  
Ion Channels ◽  
Potassium Channel ◽  
Voltage Sensitivity

scholarly journals Voltage-dependent gating and gating charge measurements in the Kv1.2 potassium channel

2015 ◽  
Vol 145 (4) ◽  
pp. 345-358 ◽  
Author(s):  
Itzel G. Ishida ◽  
Gisela E. Rangel-Yescas ◽  
Julia Carrasco-Zanini ◽  
León D. Islas
Keyword(s):  
Ion Channels ◽  
Potassium Channel ◽  
Structural Data ◽  
Activation Mechanism ◽  
Voltage Sensitivity ◽  
Structural Interpretation ◽  
Kv Channel ◽  
Gating Charge ◽  
Voltage Dependent ◽  
Electrophysiological Findings

Much has been learned about the voltage sensors of ion channels since the x-ray structure of the mammalian voltage-gated potassium channel Kv1.2 was published in 2005. High resolution structural data of a Kv channel enabled the structural interpretation of numerous electrophysiological findings collected in various ion channels, most notably Shaker, and permitted the development of meticulous computational simulations of the activation mechanism. The fundamental premise for the structural interpretation of functional measurements from Shaker is that this channel and Kv1.2 have the same characteristics, such that correlation of data from both channels would be a trivial task. We tested these assumptions by measuring Kv1.2 voltage-dependent gating and charge per channel. We found that the Kv1.2 gating charge is near 10 elementary charges (eo), ∼25% less than the well-established 13–14 eo in Shaker. Next, we neutralized positive residues in the Kv1.2 S4 transmembrane segment to investigate the cause of the reduction of the gating charge and found that, whereas replacing R1 with glutamine decreased voltage sensitivity to ∼50% of the wild-type channel value, mutation of the subsequent arginines had a much smaller effect. These data are in marked contrast to the effects of charge neutralization in Shaker, where removal of the first four basic residues reduces the gating charge by roughly the same amount. In light of these differences, we propose that the voltage-sensing domains (VSDs) of Kv1.2 and Shaker might undergo the same physical movement, but the septum that separates the aqueous crevices in the VSD of Kv1.2 might be thicker than Shaker’s, accounting for the smaller Kv1.2 gating charge.

scholarly journals Designer and natural peptide toxin blockers of the KcsA potassium channel identified by phage display

2015 ◽  
Vol 112 (50) ◽  
pp. E7013-E7021 ◽  
Author(s):  
Ruiming Zhao ◽  
Hui Dai ◽  
Netanel Mendelman ◽  
Luis G. Cuello ◽  
Jordan H. Chill ◽  
...  
Keyword(s):  
Phage Display ◽  
Potassium Channel ◽  
Lipid Bilayers ◽  
Disulfide Bonds ◽  
3D Structure ◽  
Structural Basis ◽  
Voltage Sensitivity ◽  
Type I ◽  
High Affinity ◽  
Kv1.3 Channels

Peptide neurotoxins are powerful tools for research, diagnosis, and treatment of disease. Limiting broader use, most receptors lack an identified toxin that binds with high affinity and specificity. This paper describes isolation of toxins for one such orphan target, KcsA, a potassium channel that has been fundamental to delineating the structural basis for ion channel function. A phage-display strategy is presented whereby ∼1.5 million novel and natural peptides are fabricated on the scaffold present in ShK, a sea anemone type I (SAK1) toxin stabilized by three disulfide bonds. We describe two toxins selected by sorting on purified KcsA, one novel (Hui1, 34 residues) and one natural (HmK, 35 residues). Hui1 is potent, blocking single KcsA channels in planar lipid bilayers half-maximally (Ki) at 1 nM. Hui1 is also specific, inhibiting KcsA-Shaker channels in Xenopus oocytes with a Ki of 0.5 nM whereas Shaker, Kv1.2, and Kv1.3 channels are blocked over 200-fold less well. HmK is potent but promiscuous, blocking KcsA-Shaker, Shaker, Kv1.2, and Kv1.3 channels with Ki of 1–4 nM. As anticipated, one Hui1 blocks the KcsA pore and two conserved toxin residues, Lys21 and Tyr22, are essential for high-affinity binding. Unexpectedly, potassium ions traversing the channel from the inside confer voltage sensitivity to the Hui1 off-rate via Arg23, indicating that Lys21 is not in the pore. The 3D structure of Hui1 reveals a SAK1 fold, rationalizes KcsA inhibition, and validates the scaffold-based approach for isolation of high-affinity toxins for orphan receptors.

scholarly journals Fine-tuning of Voltage Sensitivity of the Kv1.2 Potassium Channel by Interhelix Loop Dynamics

2013 ◽  
Vol 288 (14) ◽  
pp. 9686-9695 ◽  
Author(s):  
Rheanna Sand ◽  
Nazlee Sharmin ◽  
Carla Morgan ◽  
Warren J. Gallin
Keyword(s):  
Potassium Channel ◽  
Fine Tuning ◽  
Voltage Sensitivity ◽  
Loop Dynamics

A Simple Scanning Tunneling Microscope with Very Wide Scanning Range

1990 ◽  
Vol 48 (1) ◽  
pp. 314-315
Author(s):  
J.E. Yao ◽  
G.Y. Shang
Keyword(s):  
Integrated Circuits ◽  
Scanning Tunneling Microscope ◽  
Three Dimensional ◽  
Point Of View ◽  
Scanning Tunneling ◽  
Control Voltage ◽  
Voltage Sensitivity ◽  
Tunneling Microscope ◽  
Piezo Element ◽  
Scanning Range

Scanning Tunneling Microscope (STM) has been a powerful tool for study of surfaces in the range of about 1 micrometer. The small field of view is enough for imaging homogeneous surfaces with atomic or near-atomic resolution. If, however, integrated circuits, gratings and other small “man-made” structures have to be observed, a STM with very wide scan range, for example, 10 to 100 micrometers is needed. In most of the STMs currently in use, three-dimensional scanner are fabricated from piezoceramic stacks, tubes and beams. The maximum scanning range is restricted to about a micrometer because of the maximum allowable control voltage and piezo element dimensions. Recently, Takashima Koshi has constructed a x/y scan stage for observation of grating(1). In a similar point of view, We have designed and built a simple scanner (Fig.1), which includes a base B, a mechanical amplifying device (consisting of a spring lever S and a metal tube M), x/y driving elements D, z control piezo tube P and tip T. The relation between the displacement dx(dy) and applied voltage V for the scanner is described by the equation:dx(dy)=KV(2L+l)/2d. Where, K is the voltage sensitivity in nm/v; L and l are the lengths of M and S respectively; d is the distance between the axis of S and that of D. When L=30mm, l =8mm, d=5mm, k=60nm/v, a scan range of 120μm will be obtained.

Characterization of Mammalian Potassium Channel Genes

1991 ◽  
Author(s):  
James O. Douglass ◽  
◽  
Macdonald Christie ◽  
John P. Adelman ◽  
R. Alan North
Keyword(s):  
Potassium Channel
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