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10.1073/pnas.2119630119 http://scihub22266oqcxt.onion/10.1073/pnas.2119630119 36095216!9499596!36095216     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=36095216&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215       Proc+Natl+Acad+Sci+U+S+A 2022 ; 119 (38): e2119630119 Nephropedia Template TP {{tp|p=36095216|t=2022. A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons |pdf=|usr=}}{{36095216}} gab.com Text A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=36095216 #FOAvip Trigeminal neuralgia (TN) is a unique pain disorder characterized by intense paroxysmal facial pain within areas innervated by the trigeminal nerve. Although most cases of TN are sporadic, familial clusters of TN suggest that genetic factors may contribute to this disorder. Whole-exome sequencing in patients with TN reporting positive family history demonstrated a spectrum of variants of ion channels including TRP channels. Here, we used patch-clamp analysis and Ca(2+) and Na(+) imaging to assess a rare variant in the TRPM7 channel, p.Ala931Thr, within transmembrane domain 3, identified in a man suffering from unilateral TN. We showed that A931T produced an abnormal inward current carried by Na(+) and insensitive to the pore blocker Gd(3+). Hypothesizing that replacement of the hydrophobic alanine at position 931 with the more polar threonine destabilizes a hydrophobic ring, near the voltage sensor domain, we performed alanine substitutions of F971 and W972 and obtained results suggesting a role of A931-W972 hydrophobic interaction in S3-S4 hydrophobic cleft stability. Finally, we transfected trigeminal ganglion neurons with A931T channels and observed that expression of this TRPM7 variant lowers current threshold and resting membrane potential, and increases evoked firing activity in TG neurons. Our results support the notion that the TRPM7-A931T mutation located in the S3 segment at the interface with the transmembrane region S4, generates an omega current that carries Na(+) influx in physiological conditions. A931T produces hyperexcitability and a sustained Na(+) influx in trigeminal ganglion neurons that may underlie pain in this kindred with trigeminal neuralgia. Twit Text FOAVip A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=36095216 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=36095216 #FOAvip English Wikipedia <ref>{{Cite pmid|36095216}}</ref> A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons #MMPMID36095216 Gualdani R; Gailly P; Yuan JH; Yerna X; Di Stefano G; Truini A; Cruccu G; Dib-Hajj SD; Waxman SG Proc Natl Acad Sci U S A 2022[Sep]; 119 (38): e2119630119 PMID36095216show ga Trigeminal neuralgia (TN) is a unique pain disorder characterized by intense paroxysmal facial pain within areas innervated by the trigeminal nerve. Although most cases of TN are sporadic, familial clusters of TN suggest that genetic factors may contribute to this disorder. Whole-exome sequencing in patients with TN reporting positive family history demonstrated a spectrum of variants of ion channels including TRP channels. Here, we used patch-clamp analysis and Ca(2+) and Na(+) imaging to assess a rare variant in the TRPM7 channel, p.Ala931Thr, within transmembrane domain 3, identified in a man suffering from unilateral TN. We showed that A931T produced an abnormal inward current carried by Na(+) and insensitive to the pore blocker Gd(3+). Hypothesizing that replacement of the hydrophobic alanine at position 931 with the more polar threonine destabilizes a hydrophobic ring, near the voltage sensor domain, we performed alanine substitutions of F971 and W972 and obtained results suggesting a role of A931-W972 hydrophobic interaction in S3-S4 hydrophobic cleft stability. Finally, we transfected trigeminal ganglion neurons with A931T channels and observed that expression of this TRPM7 variant lowers current threshold and resting membrane potential, and increases evoked firing activity in TG neurons. Our results support the notion that the TRPM7-A931T mutation located in the S3 segment at the interface with the transmembrane region S4, generates an omega current that carries Na(+) influx in physiological conditions. A931T produces hyperexcitability and a sustained Na(+) influx in trigeminal ganglion neurons that may underlie pain in this kindred with trigeminal neuralgia. |*Protein Serine-Threonine Kinases/genetics[MESH] |*TRPM Cation Channels/genetics/metabolism[MESH] |*Trigeminal Ganglion/physiopathology[MESH] |*Trigeminal Neuralgia/genetics[MESH] |Alanine/genetics[MESH] |Humans[MESH] |Male[MESH] |Mutation[MESH]A TRPM7 mutation linked to familial trigeminal neuralgia: Omega curren(epmc).pdf DeepDyve Pubget Overpricing