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 1P375 Single-molecular gating dynamics of KcsA potassium channel measured by diffracted X-ray tracking(14. Ion channels and receptors,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

2006 ◽  
Vol 46 (supplement2) ◽  
pp. S240
Author(s):  
Hirofumi Shimizu ◽  
Masayuki Iwamoto ◽  
Fumiko Inoue ◽  
Takashi Konno ◽  
Yuji_C. Sasaki ◽  
...  
Keyword(s):  
Ion Channels ◽  
Potassium Channel ◽  
Poster Session ◽  
X Ray ◽  
Meeting Program ◽  
Kcsa Potassium Channel

scholarly journals Expression of a poriferan potassium channel: insights into the evolution of ion channels in metazoans

2009 ◽  
Vol 212 (6) ◽  
pp. 761-767 ◽  
Author(s):  
G. J. Tompkins-MacDonald ◽  
W. J. Gallin ◽  
O. Sakarya ◽  
B. Degnan ◽  
S. P. Leys ◽  
...  
Keyword(s):  
Ion Channels ◽  
Potassium Channel

scholarly journals Further studies of ion channels in the electroreceptor of the skate through deep sequencing, cloning and cross species comparisons

2018 ◽  
Author(s):  
William T. Clusin ◽  
Ting-Hsuan Wu ◽  
Ling-Fang Shi ◽  
Peter N. Kao
Keyword(s):  
Amino Acids ◽  
Ion Channels ◽  
Potassium Channel ◽  
Calcium Channel ◽  
Beta Subunit ◽  
K Channel ◽  
Rna Seq ◽  
Α Subunit ◽  
Accessory Subunits ◽  
Voltage Dependent

AbstractOur comparative studies seek to understand the structure and function of ion channels in cartilaginous fish that can detect very low voltage gradients in seawater. The principal channels of the electroreceptor include a calcium activated K channel, whose α subunit is Kcnma1, a voltage-dependent calcium channel, Cacna1d, and a relatively uncharacterized K channel which interacts with the calcium channel to produce fast (20 Hz) oscillations. Large conductance calcium-activated K channels (BK) are comprised of four α subunits, encoded by Kcnma1 and modulatory β subunits of the Kcnmb class. We recently cloned and published the skate Kcnma1 gene and most of Kcnmb4 derived from using purified mRNA of homogenized isolated electroreceptors. Bellono et al. have recently performed RNA sequencing (RNA-seq) on purified mRNA from skate electroreceptors and found several ion channels including Kcnma1. We searched the the Bellono et al RNA-seq repository for additional channels and subunits. Our most significant findings are the presence of two Shaker type voltage dependent potassium channel sequences which are grouped together as isoforms in the data repository. The larger of these is a skate ortholog of the voltage dependent fast potassium channel Kv1.1, which is expressed at appreciable levels and seems likely to explain the 20 Hz oscillations believed to occur in vivo. The second was more similar to Kv1.5 than to Kv1.1 but was somewhat atypical. We also found a beta subunit sequence (Kcnab2) which appears not to cause fast inactivation due to specific structural features. The new channels and subunits were verified by RT-PCR and the Kv1.1 sequence was confirmed by cloning. We also searched the RNA-seq repository for accessory subunits of the calcium activated potassium channel, Kcnma1, and found a computer generated assembly that contained a complete sequence of its beta subunit, Kcnmb2. Skate Kcnmb2 has a total of 279 amino acids, with 51 novel amino acids at the N-terminus which may play a specific physiological role. This sequence was confirmed by PCR and cloning. However, skate Kcnmb2 is expressed at low levels in the electroreceptor compared to Kcnma1 and skate Kcnmb1 (beta1) is absent. The evolutionary origin of the newly described channels and subunits was studied by aligning skate sequences with human sequences and those found in related fish: the whale shark (R. typus) an elasmobranch, and ghost shark (C.milii). There is also homology with the lamprey, which has electroreceptors. An evolutionary tree is presented. Further research should include focusing on the subcellular locations of these channels in the receptor cells, their gating behavior, and the effects of accessory subunits on gating.

scholarly journals Gain-of-Function Mutations in the Transient Receptor Potential Channels TRPV1 and TRPA1: How Painful?

2014 ◽  
pp. S205-S213 ◽  
Author(s):  
S. BOUKALOVA ◽  
F. TOUSKA ◽  
L. MARSAKOVA ◽  
A. HYNKOVA ◽  
L. SURA ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Pain Syndrome ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Single Amino Acid ◽  
Voltage Sensitivity ◽  
Gain Of Function ◽  
Potential Channels ◽  
Transient Receptor

Gain-of-function (GOF) mutations in ion channels are rare events, which lead to increased agonist sensitivity or altered gating properties, and may render the channel constitutively active. Uncovering and following characterization of such mutants contribute substantially to the understanding of the molecular basis of ion channel functioning. Here we give an overview of some GOF mutants in polymodal ion channels specifically involved in transduction of painful stimuli – TRPV1 and TRPA1, which are scrutinized by scientists due to their important role in development of some pathological pain states. Remarkably, a substitution of single amino acid in the S4-S5 region of TRPA1 (N855S) has been recently associated with familial episodic pain syndrome. This mutation increases chemical sensitivity of TRPA1, but leaves the voltage sensitivity unchanged. On the other hand, mutations in the analogous region of TRPV1 (R557K and G563S) severely affect all aspects of channel activation and lead to spontaneous activity. Comparison of the effects induced by mutations in homologous positions in different TRP receptors (or more generally in other distantly related ion channels) may elucidate the gating mechanisms conserved during evolution.

scholarly journals Differential roles of trithorax protein MLL-1 in regulating neuronal Ion channels

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Dave Sonya ◽  
Zhou An
Keyword(s):  
Ion Channels ◽  
Potassium Channel ◽  
Polycomb Group ◽  
Channel Activity ◽  
Sodium Currents ◽  
Trithorax Group ◽  
Channel Protein ◽  
Trxg Protein ◽  
First Time ◽  
Potassium Channel Activity

Repressive regulation of potassium channel genes by Polycomb group (PcG) proteins contributes to PcG protein-mediated neuroprotection against neuronal ischemic injury, as seen in an ischemic stroke. Here we asked the question whether Trithorax group (TrxG) proteins, the antagonistic partners of PcG proteins (i.e, epigenetic activators targeting the same genes) may also regulate potassium channels. Results of patch-clamp studies on cultured neuronal cells showed that inhibition of TrxG protein MLL-1 led to an increase in potassium channel activity, an unexpected effect for a presumed gene activator. In contrast, decreased sodium currents were observed with MLL-1 inhibition. Increased or decreased levels of potassium channel protein Kv2.1 or sodium channel protein Nav1.2, respectively, were seen with MLL-1 inhibition, as determined by immunocytochemistry. These results, for the first time, demonstrate an involvement of TrxG protein MLL-1 in regulating neuronal ion channels, potentially repressing potassium channel genes.

scholarly journals Molecular basis for voltage sensitivity in membrane proteins

2018 ◽  
Author(s):  
Marina A. Kasimova ◽  
Erik Lindahl ◽  
Lucie Delemotte
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Membrane Proteins ◽  
Voltage Sensitivity ◽  
Voltage Sensing ◽  
Suggested Approach ◽  
Voltage Gated ◽  
Living Organisms ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

ABSTRACTVoltage-sensitive membrane proteins are united by the ability to transform changes in the membrane potential into mechanical work. They are responsible for a spectrum of key physiological processes in living organisms, including electric signaling and progression along the cell cycle. While the voltage-sensing mechanism has been well characterized for some membrane proteins such as voltage-gated ion channels, for others even the location of the voltage-sensing elements remains unknown. The detection of these elements using experimental techniques is complicated due to the large diversity of membrane proteins. Here, we suggest a computational approach to predict voltage-sensing elements in any membrane protein independent of structure or function. It relies on the estimation of the capacity of a protein to respond to changes in the membrane potential. We first show how this property correlates well with voltage sensitivity by applying our approach to a set of membrane proteins including voltage-sensitive and voltage-insensitive ones. We further show that it correctly identifies true voltage-sensitive residues in the voltage sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions potentially involved in the response to voltage. The suggested approach is fast and simple and allows for characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application prior to mutagenesis experiments will allow for significant reduction of the number of potential voltage-sensitive elements to be tested.

Sign in / Sign up

Export Citation Format

Share Document