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  • currents
  • We tested the hypothesis that these toxins could function as blockers of the pathogenic gating pore currents. (ugent.be)
  • This disease is caused by genetic mutation that leads to the occurrence of the so-called ω-currents or leakage currents via voltage-gated ion channels Nav1.4 in skeletal muscles. (scienmag.com)
  • We are the first to prove that there are natural chemical compounds able to block the leakage currents through mutated channels,' explained Mikhail Petrovich Kirpichnikov, Doctor of Biological Sciences, member of the Russian Academy of Sciences, and dean of the Faculty of Biology, MSU. (scienmag.com)
  • Calmodulin also was able to modulate the inactivation kinetics of Nav1.6, but not Nav1.4, currents in a calcium-dependent manner. (epfl.ch)
  • Ranzoline blocks Na+ currents of Nav1.4. (epfl.ch)
  • We suggest that Hm-3 binding to these charged groups inhibits voltage sensor transition to the activated state and blocks the depolarization-activated gating pore currents. (frontiersin.org)
  • For over 40 y, these rearrangements have been recorded as "gating" currents, the intensities and kinetics of which are unique signatures of VGCC function. (pnas.org)
  • These so-called gating currents have been investigated extensively within the theoretical framework of so-called discrete-state Markov models (DMMs), whereby activation is conceptualized as a series of transitions across a discrete set of states. (pnas.org)
  • Inward sodium currents through the gating pore of mutant R666G are only approximately 1% of central pore current, but substitution of guanidine for sodium in the extracellular solution increases their size by 13- +/- 2-fold. (nih.gov)
  • Gating pore currents in R666G at depolarized and hyperpolarized holding potentials. (nih.gov)
  • Currents were recorded in the presence of 1 µM TTX in response to a series of 50-ms voltage steps ranging from −160 mV to 50 mV in 5-mV increments from a holding potential of −100 mV (left panels and black symbols) or 0 mV (right panels and red symbols) without any leak subtraction. (nih.gov)
  • Currents through the wild-type Na V 1.4 (A) and R666G (B) channels are shown on a scale where both gating charge displacement and gating pore currents can be observed and compared. (nih.gov)
  • C) Records from B are shown on an expanded scale, focusing on gating pore currents. (nih.gov)
  • pore formed
  • Similar to Kv channels, the BK channels are homotetramers with the central pore formed by S5 to S6 transmembrane segments from all four subunits and voltage sensor domains (VSDs) containing S1-S4 transmembrane segments. (jneurosci.org)
  • Guanidine is also highly permeant through the proton-selective gating pore formed by the mutant R666H. (nih.gov)
  • inward
  • It acts by shifting the voltage dependence of channel activation to more depolarized potentials and by blocking the inward component of the sodium current (PubMed:16267209). (rcsb.org)
  • extensively
  • Although vertebrate Nav function has been extensively studied, the detailed structural basis for voltage-dependent gating mechanisms remain obscure. (edu.au)
  • dependence of channel
  • the other is to regulate coupling among the activation gate, voltage sensor, and Ca 2+ binding via electrostatic interactions with E321/E324 located in the cytosolic side of S6 in a neighboring subunit, resulting in a shift of the voltage dependence of channel opening and increased Ca 2+ sensitivity. (jneurosci.org)
  • periodic paralyses
  • To test whether these periodic paralyses might be treated by blocking gating pore current, we screened several aromatic and aliphatic guanidine derivatives and found that 1-(2,4-xylyl)guanidinium can block gating pore current in the millimolar concentration range without affecting normal Na(V)1.4 channel function. (nih.gov)
  • activation
  • The opening of these ion channels includes three general molecular processes: activation of the sensor, propagation of the conformational changes in the sensor to the pore, and the opening of the pore. (jneurosci.org)
  • Our results bridge the gap between microscopic and macroscopic descriptions of activation dynamics and show that choosing the gating charge as reaction coordinate masks the topological complexity of the network of microstates participating in the transition. (pnas.org)
  • homology
  • Here we attempt to contribute to this theory by simulating access and binding of LAs in the KcsA-based homology model of the closed Na + channel. (aspetjournals.org)
  • mutation
  • Using a range of genetic methods, protein engineering, electrophysiology, NMR spectroscopy, and computer modeling, the scientists studied the reasons for abnormal activities in the channels damaged by mutation. (scienmag.com)
  • extracellular
  • Local anesthetics (LAs) are known to bind Na + channels in the closed, open, and inactivated states and reach their binding sites via extracellular and intracellular access pathways. (aspetjournals.org)
  • Xenopus
  • Functional Nav-LBT channels expressed in Xenopus oocytes were voltage-clamped, and distinct LRET signals were obtained in the resting and slow inactivated states. (edu.au)