• To evaluate the Swarm screening system, we optimized a series of heterologous optogenetic spiking HEK293 cell assays for several voltage-gated sodium channel subtypes including Nav1.2, Nav1.5, and Nav1.7. (frontiersin.org)
  • Genetic etiology of PE is mutations on SCN9A , the encoding gene of a voltage-gated sodium channel subtype Nav1.7. (biomedcentral.com)
  • Novel drugs such as PF-05089771 and TV-45070 could be promising in ameliorating pain symptoms due to their Nav1.7 selectivity. (biomedcentral.com)
  • This review mainly focuses on PE and the causative gene SCN9A -- its mutations and their effects on Nav1.7 channels' electrophysiological properties. (biomedcentral.com)
  • The causative gene for PE, SCN9A , encodes a voltage-gated sodium channel (VGSC) subtype Nav1.7. (biomedcentral.com)
  • PE is exclusively caused by mutations in SCN9A , the encoding gene of sodium channel subtype Nav1.7 and can be sub-classified into familial (inherited erythromelalgia) and sporadic forms. (biomedcentral.com)
  • In response to an increase of the membrane potential to about −55 mV (in this case, caused by an action potential), the activation gates open, allowing positively charged Na+ ions to flow into the neuron through the channels, and causing the voltage across the neuronal membrane to increase to +30 mV in human neurons. (wikipedia.org)
  • At the peak of the action potential, when enough Na+ has entered the neuron and the membrane's potential has become high enough, the Na+ channels inactivate themselves by closing their inactivation gates. (wikipedia.org)
  • With the Na+ channel no longer contributing to the membrane potential, the potential decreases back to its resting potential as the neuron repolarizes and subsequently hyperpolarizes itself, and this constitutes the falling phase of an action potential. (wikipedia.org)
  • ELP caused cortical hyperexcitability at P8-9 as assessed via multi-electrode array recordings that coincided with reduced expression of synaptic genes (RNAseq) including Grin2b , neurexins, piccolo and voltage gated calcium and sodium channels. (biomedcentral.com)
  • To address this challenge, we developed the Swarm TM , a custom designed optical instrument for highly parallelized, multicolor measurements in excitable cells, simultaneously recording changes in voltage and calcium activities at high temporal resolution under optical stimulation. (frontiersin.org)
  • Sodium channels are highly selective for the transport of ions across cell membranes. (wikipedia.org)
  • The highly conserved S4 segment acts as the channel's voltage sensor. (wikipedia.org)
  • When stimulated by a change in transmembrane voltage, this segment moves toward the extracellular side of the cell membrane, allowing the channel to become permeable to ions. (wikipedia.org)
  • The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥ 2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). (bvsalud.org)
  • Sodium channels consist of large alpha subunits that associate with accessory proteins, such as beta subunits. (wikipedia.org)
  • When the alpha subunit protein is expressed by a cell, it is able to form a pore in the cell membrane that conducts Na+ in a voltage-dependent way, even if beta subunits or other known modulating proteins are not expressed. (wikipedia.org)
  • Optogenetic assays provide a flexible, scalable, and information rich approach to probe compound effects for ion channel drug targets in both heterologous expression systems and associated disease relevant cell types. (frontiersin.org)
  • Open in a separate window Figure 5 Model demonstrating the mechanisms of TBK1 mediated mTOR regulation. (healthweblognews.info)
  • An alpha subunit forms the core of the channel and is functional on its own. (wikipedia.org)
  • The inactivation gate can be thought of as a "plug" tethered to domains III and IV of the channel's intracellular alpha subunit. (wikipedia.org)
  • Voltage-gated Na+ channels have three main conformational states: closed, open and inactivated. (wikipedia.org)
  • All involve encapsulation of the sodium ion in a cavity of specific size within a larger molecule. (wikipedia.org)
  • Essentially opposite paths in fetal brain development may explain two major subtypes of autism. (epiphanyasd.com)
  • Closure of the inactivation gate causes Na+ flow through the channel to stop, which in turn causes the membrane potential to stop rising. (wikipedia.org)
  • That in turn could explain why drug treatments for autism so far are failing. (epiphanyasd.com)