• Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K + ion occupancy, and K + conductance. (nature.com)
  • We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history. (uantwerpen.be)
  • His ensuing studies included the computation of the multi-ion free energy landscape to explain the atomic basis of the knock-on mechanism of ion conduction proposed decades earlier by Hodgkin and Keynes (1955). (biophysicalsociety.ca)
  • OBJECTIVES: To observe the therapeutic effect of electroacupuncture (EA) on neurogenic urinary retention rats, so as to explore the underlying mechanism of EA in treating neurogenic urinary retention by focusing on 3-phosphoinositide-dependent protein kinase 1 (PDK1)/protein kinase B (Akt)/hyperpolarization activated cyclic nucleotide-gated cation channel 4 (HCN4) pathway. (bvsalud.org)
  • Does grain size have an influence on intrinsic mechanical properties and conduction mechanism of near fully-dense boron carbide ceramics? (us.es)
  • but also has critical effects on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. (frontiersin.org)
  • By leveraging fluorescence lifetime imaging microscopy (FLIM) and Förster resonance energy transfer (FRET), we visualized the localization of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in membrane domains. (bvsalud.org)
  • MTX occludes the pore region of various potassium channels (Kv1.2, IKCa1, Kv1.3) by establishing strong interactions between its lysine-23 residue and the glycine-tyrosine-glycine-aspartate (GYGD) motif of the channel. (wikipedia.org)
  • Although Kv1.1, Kv1.2, and Kv1.3 have a very similar pore structure, they display different pharmacological sensitivity to MTX. (wikipedia.org)
  • Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. (uantwerpen.be)
  • MTX thus blocks the channels by binding in the external vestibule of the pore to block the ion conduction pathway. (wikipedia.org)
  • He went on to show that the driving force for ion flux arising from the membrane potential is focused along the narrow pore (Roux et al, 2000). (biophysicalsociety.ca)
  • During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K+ conduction through constriction of the K+ selectivity filter. (uantwerpen.be)
  • They culminated in his prediction of the five main cation binding sites along the selectivity filter of the KcsA potassium channel (Berneche and Roux, 2001) that were then observed independently and experimentally in high resolution crystallographic structures (Zhou et al, 2001). (biophysicalsociety.ca)
  • Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. (nature.com)
  • Kir channels consist of only two transmembrane helices plus an extensive C-terminal cytoplasmic tail of the channel pore. (nature.com)
  • 2005. Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement. (biophysicalsociety.ca)
  • Limited knowledge exists regarding the response of voltage-gated ion channels to transmembrane potential within distinct membrane compartments. (bvsalud.org)
  • Kuo, 1998 ), but the molecular identities of these channels are unknown. (jneurosci.org)
  • The determination of the structure of the KcsA potassium channel Doyle et al (1998) provided the opportunity to extend and apply his methods to the much more challenging problem of a biologically-selective channel. (biophysicalsociety.ca)
  • The intermediate conductance Ca2+-activated K+ (IK) channel is present in peripheral tissues, including secretory epithelia and blood cells. (wikipedia.org)
  • Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. (wikipedia.org)
  • The Ca2+-activated K+ channel of intermediate conductance:a possible target for immune suppression. (wikipedia.org)
  • Ion channel gating and conductance are classically understood as separate processes. (nature.com)
  • The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as 'gated' substates. (nature.com)
  • In the G178D structure, the HBC gate is slightly wider than in previous structures, and molecular dynamics (MD) simulations demonstrate rapid wetting of the G178D pore at the HBC region, followed by further expansion and K + conductance through the channel. (nature.com)
  • Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. (uantwerpen.be)
  • Brownian dynamics simulations of the recognition of the scorpion toxin maurotoxin with the voltage-gated potassium ion channels. (wikipedia.org)
  • His most significant and highly recognized work has established the physical principles that govern the function of the physiologically critical ion channels and integral membrane proteins, largely through his highly creative molecular dynamics simulations of biomembranes. (biophysicalsociety.ca)
  • His simulations showed that the water-filled vestibular cavity at the intracellular entrance of the KcsA channel achieved its selectivity for monovalent cations from an unusual and unexpected balance of the electrostatic reaction field (Roux and MacKinnon, 1999). (biophysicalsociety.ca)
  • Initial repolarization (phase 1) is mediated by the opening of transient outward K + channels (I to ). (alomone.com)
  • Mutations in the genes encoding a calcium channel (Ca V 1.1) and a sodium channel (Na V 1.4) have been identified in HypoPP families. (jci.org)
  • Here we report that the behavioral defects in the C. elegans egl-2 mutant are caused by a gain-of-function ( gf ) mutation in an eag-like K + channel. (jneurosci.org)
  • Mutant EGL-2( gf ) channels exhibited a negative shift in voltage dependence of activation, and both wild-type (WT) and mutant currents were blocked by imipramine. (jneurosci.org)
  • Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. (nature.com)
  • We reported the crystal structure of a chicken Kir2.2[G178D] mutant channel 12 , in which the introduced G178D mutations at the HBC functionally stabilize the open conformation, a strategy used previously to obtain an open crystal structure of a bacterial homolog KirBac3.1 13 . (nature.com)
  • To address the question of specificity for the allele encoding the Na V 1.4-R669H variant as a cause of HypoPP and to produce a model system in which to characterize functional defects of the mutant channel and susceptibility to paralysis, we generated knockin mice carrying the ortholog of the gene encoding the Na V 1.4-R669H variant (referred to herein as R669H mice). (jci.org)
  • Potassium channels are present in all types of cells and play critical roles in control of multiple physiological processes. (nature.com)
  • Suppression of egl-2(gf) phenotypes by imipramine likely results from the block of EGL-2( gf ) channels. (jneurosci.org)
  • Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. (nature.com)
  • Behavioral and pharmacological studies of these mutants may provide insight into the genetic and mechanistic basis of K + channel dysfunction in vivo . (jneurosci.org)
  • The molecular mechanisms leading to the development of heart diseases are associated with impaired permeability and excitability of cell membranes and are mainly caused by the dysfunction of cardiac Ca2+ channels. (bvsalud.org)
  • We hypothesize that EGL-2( gf ) channels cause behavioral defects through suppression of excitability in critical cells. (jneurosci.org)
  • The initial upstroke of the cardiac action potential is determined by the opening and closing of Na + channels (phase 0). (alomone.com)
  • Most of these diseases are characterized by cardiac arrhythmias, conduction, and contractility disorders. (bvsalud.org)
  • The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo and in situ. (bvsalud.org)
  • The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. (bvsalud.org)
  • Molecular coupling between voltage sensing and gating in Kv-channels. (uantwerpen.be)
  • The configuration and rate of repolarization of action potentials are controlled by many types of K + channel currents that differ with respect to their kinetics, density of the channels in the plasma membrane and their location in the heart. (alomone.com)
  • An important physiological role of the IK channel is to help maintain large electrical gradients for the sustained transport of ions such as Ca2+ that controls T lymphocyte (T cell) proliferation. (wikipedia.org)
  • The urodynamic indexes of rats were detected by multi-channel physiological recorderï¼ muscle strip test was used to detect detrusor excitabilityï¼ the morphological changes of bladder were observed by HE staining. (bvsalud.org)
  • In the present study, we carry out detailed single-channel analyses of cKir2.2[G178D] and hKir2.1[G177E] channels that reveal striking sub-state gating behavior. (nature.com)
  • This implicates expansion of the HBC as a critical step in Kir channel opening, as seen in a recent Kir6.2 structure 11 . (nature.com)
  • To fabricate NGC with similar structure to extracellular membrane (ECM), the physiochemical, mechanical and biological properties of the materials such as biocompatibility, biodegradability, mechanical properties, minimum swelling and inflammation as well as desirable nerve conduction are important4,5,6. (yjxinhua.com)
  • Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. (uantwerpen.be)
  • We show that the Caenorhabditis elegans egl-2 gene encodes an eag K + channel and that a gain-of-function mutation in egl-2 blocks excitation in neurons and muscles by causing the channel to open at inappropriately negative voltages. (jneurosci.org)
  • He showed that in contrast to this view, selectivity in the KcsA channel is controlled by the properties of the flexible carbonyl ligands that line the walls of the channel. (biophysicalsociety.ca)
  • Scorpion toxins constitute the largest group of potassium (K+) channel blockers and are useful pharmacological probes to investigate ion channels and their functions. (wikipedia.org)
  • The K+ permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). (uantwerpen.be)
  • K + channels are key regulators of cellular excitability. (jneurosci.org)
  • Ion channels function within a membrane environment characterized by dynamic lipid compartmentalization. (bvsalud.org)
  • Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular cells. (bvsalud.org)
  • Similar inhibition is observed with the mouse homolog MEAG, suggesting that inhibition of EAG-like channels may mediate some clinical side effects of this class of antidepressants. (jneurosci.org)
  • Using a self-stimulated neural conductive channel to create a suitable scaffold for the growth and differentiation of neural-like cells can be desirable20. (yjxinhua.com)