SCN9A
Nav1.7 jest natrijski kanal koji je kod ljudi kodiran genom SCN9A sa hromosoma 2.[5][6][7] Obično se eksprimira na visokim nivoima u dva tipa neurona: nociceptivnim (bolnim) neuronima u ganglijskom dorzalnom korijenu (DRG), rigeninusnoj gangliji i neuronima simpatičkih ganglija , koji su dio autonomnog (nevoljnog) nervnog sistema.[8][9]
Aminokiselinska sekvenca uredi
Dužina polipeptidnog lanca je 1.988 aminokiselina, a molekulska masa 226.372 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAMLPPPGPQ | SFVHFTKQSL | ALIEQRIAER | KSKEPKEEKK | DDDEEAPKPS | ||||
| SDLEAGKQLP | FIYGDIPPGM | VSEPLEDLDP | YYADKKTFIV | LNKGKTIFRF | ||||
| NATPALYMLS | PFSPLRRISI | KILVHSLFSM | LIMCTILTNC | IFMTMNNPPD | ||||
| WTKNVEYTFT | GIYTFESLVK | ILARGFCVGE | FTFLRDPWNW | LDFVVIVFAY | ||||
| LTEFVNLGNV | SALRTFRVLR | ALKTISVIPG | LKTIVGALIQ | SVKKLSDVMI | ||||
| LTVFCLSVFA | LIGLQLFMGN | LKHKCFRNSL | ENNETLESIM | NTLESEEDFR | ||||
| KYFYYLEGSK | DALLCGFSTD | SGQCPEGYTC | VKIGRNPDYG | YTSFDTFSWA | ||||
| FLALFRLMTQ | DYWENLYQQT | LRAAGKTYMI | FFVVVIFLGS | FYLINLILAV | ||||
| VAMAYEEQNQ | ANIEEAKQKE | LEFQQMLDRL | KKEQEEAEAI | AAAAAEYTSI | ||||
| RRSRIMGLSE | SSSETSKLSS | KSAKERRNRR | KKKNQKKLSS | GEEKGDAEKL | ||||
| SKSESEDSIR | RKSFHLGVEG | HRRAHEKRLS | TPNQSPLSIR | GSLFSARRSS | ||||
| RTSLFSFKGR | GRDIGSETEF | ADDEHSIFGD | NESRRGSLFV | PHRPQERRSS | ||||
| NISQASRSPP | MLPVNGKMHS | AVDCNGVVSL | VDGRSALMLP | NGQLLPEVII | ||||
| DKATSDDSGT | TNQIHKKRRC | SSYLLSEDML | NDPNLRQRAM | SRASILTNTV | ||||
| EELEESRQKC | PPWWYRFAHK | FLIWNCSPYW | IKFKKCIYFI | VMDPFVDLAI | ||||
| TICIVLNTLF | MAMEHHPMTE | EFKNVLAIGN | LVFTGIFAAE | MVLKLIAMDP | ||||
| YEYFQVGWNI | FDSLIVTLSL | VELFLADVEG | LSVLRSFRLL | RVFKLAKSWP | ||||
| TLNMLIKIIG | NSVGALGNLT | LVLAIIVFIF | AVVGMQLFGK | SYKECVCKIN | ||||
| DDCTLPRWHM | NDFFHSFLIV | FRVLCGEWIE | TMWDCMEVAG | QAMCLIVYMM | ||||
| VMVIGNLVVL | NLFLALLLSS | FSSDNLTAIE | EDPDANNLQI | AVTRIKKGIN | ||||
| YVKQTLREFI | LKAFSKKPKI | SREIRQAEDL | NTKKENYISN | HTLAEMSKGH | ||||
| NFLKEKDKIS | GFGSSVDKHL | MEDSDGQSFI | HNPSLTVTVP | IAPGESDLEN | ||||
| MNAEELSSDS | DSEYSKVRLN | RSSSSECSTV | DNPLPGEGEE | AEAEPMNSDE | ||||
| PEACFTDGCV | WRFSCCQVNI | ESGKGKIWWN | IRKTCYKIVE | HSWFESFIVL | ||||
| MILLSSGALA | FEDIYIERKK | TIKIILEYAD | KIFTYIFILE | MLLKWIAYGY | ||||
| KTYFTNAWCW | LDFLIVDVSL | VTLVANTLGY | SDLGPIKSLR | TLRALRPLRA | ||||
| LSRFEGMRVV | VNALIGAIPS | IMNVLLVCLI | FWLIFSIMGV | NLFAGKFYEC | ||||
| INTTDGSRFP | ASQVPNRSEC | FALMNVSQNV | RWKNLKVNFD | NVGLGYLSLL | ||||
| QVATFKGWTI | IMYAAVDSVN | VDKQPKYEYS | LYMYIYFVVF | IIFGSFFTLN | ||||
| LFIGVIIDNF | NQQKKKLGGQ | DIFMTEEQKK | YYNAMKKLGS | KKPQKPIPRP | ||||
| GNKIQGCIFD | LVTNQAFDIS | IMVLICLNMV | TMMVEKEGQS | QHMTEVLYWI | ||||
| NVVFIILFTG | ECVLKLISLR | HYYFTVGWNI | FDFVVVIISI | VGMFLADLIE | ||||
| TYFVSPTLFR | VIRLARIGRI | LRLVKGAKGI | RTLLFALMMS | LPALFNIGLL | ||||
| LFLVMFIYAI | FGMSNFAYVK | KEDGINDMFN | FETFGNSMIC | LFQITTSAGW | ||||
| DGLLAPILNS | KPPDCDPKKV | HPGSSVEGDC | GNPSVGIFYF | VSYIIISFLV | ||||
| VVNMYIAVIL | ENFSVATEES | TEPLSEDDFE | MFYEVWEKFD | PDATQFIEFS | ||||
| KLSDFAAALD | PPLLIAKPNK | VQLIAMDLPM | VSGDRIHCLD | ILFAFTKRVL | ||||
| GESGEMDSLR | SQMEERFMSA | NPSKVSYEPI | TTTLKRKQED | VSATVIQRAY | ||||
| RRYRLRQNVK | NISSIYIKDG | DRDDDLLNKK | DMAFDNVNEN | SSPEKTDATS | ||||
| STTSPPSYDS | VTKPDKEKYE | QDRTEKEDKG | KDSKESKK |
Funkcija uredi
Nav1.7 je naponski vođeni natrijski kanal i igra ključnu ulogu u stvaranju i provođenju akcijskih potencijala i stoga je važanza električnu signalizaciju većine ekscitabilnih ćelija. Nav1.7 je prisutan na završecima nerava koji osjećaju bol, nociceptorima, blizu regije gdje je impuls pokrenut. Stimulacija nervnih završetaka nociceptora proizvodi "generatorske potencijale", koji su male promjene napona kroz neuronske membrane. Nav1.7 kanal pojačava ove membranske depolarizacije, a kada razlika membranskog potencijala dostigne određeni prag, neuron se aktivira. U senzornim neuronima, višestruke natrijeve struje zavisne od napona mogu se razlikovati po njihovoj ovisnosti o naponu i po osjetljivosti na blokator natrijskih kanala ([tetrodotoksin]). Nav1.7 kanal proizvodi brzo aktivirajuću i inaktivirajuću struju koja je osjetljiva na nivo tetrodotoksina.[10] Nav1.7 je važan u ranim fazama neuronske elektrogeneze. Aktivnost Nav1.7 sastoji se od sporog prijelaza kanala u neaktivno stanje kada je depolariziran, čak i u manjem stepenu.[11] Ovo svojstvo omogućava da ovi kanali ostanu dostupni za aktivaciju čak i sa malim ili sporo razvijajućim depolarizacijama. Stimulacija nervnih završetaka nociceptora proizvodi "generatorske potencijale", male promjene u naponu na neuronskim membranama.[11] Ovo dovodi neurone do napona koji stimulira Nav1,8, koji ima više depolarizovani prag aktivacije koji proizvodi većinu transmembranske struje, odgovorne za depolarizirajuću fazu akcijskih potencijala.[12]
Reference uredi
- ^ a b c GRCh38: Ensembl release 89: ENSG00000169432 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000075316 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Klugbauer N, Lacinova L, Flockerzi V, Hofmann F (mart 1995). "Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells". The EMBO Journal. 14 (6): 1084–90. doi:10.1002/j.1460-2075.1995.tb07091.x. PMC 398185. PMID 7720699.
- ^ Plummer NW, Meisler MH (april 1999). "Evolution and diversity of mammalian sodium channel genes". Genomics. 57 (2): 323–31. doi:10.1006/geno.1998.5735. PMID 10198179.
- ^ Catterall WA, Goldin AL, Waxman SG (decembar 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacological Reviews. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098. S2CID 7332624.
- ^ a b Raymond CK, Castle J, Garrett-Engele P, Armour CD, Kan Z, Tsinoremas N, Johnson JM (oktobar 2004). "Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia". The Journal of Biological Chemistry. 279 (44): 46234–41. doi:10.1074/jbc.M406387200. PMID 15302875.
- ^ Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG (maj 2006). "A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons". Proceedings of the National Academy of Sciences of the United States of America. 103 (21): 8245–50. Bibcode:2006PNAS..103.8245R. doi:10.1073/pnas.0602813103. PMC 1472458. PMID 16702558.
- ^ Catterall WA (2000). "Structure and regulation of voltage-gated Ca2+ channels". Annual Review of Cell and Developmental Biology. 16: 521–55. doi:10.1146/annurev.cellbio.16.1.521. PMID 11031246.
- ^ a b Cummins TR, Howe JR, Waxman SG (decembar 1998). "Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel". The Journal of Neuroscience. 18 (23): 9607–19. doi:10.1523/JNEUROSCI.18-23-09607.1998. PMC 6793269. PMID 9822722.
- ^ Renganathan M, Cummins TR, Waxman SG (august 2001). "Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons". Journal of Neurophysiology. 86 (2): 629–40. doi:10.1152/jn.2001.86.2.629. PMID 11495938. S2CID 11579149.
Dopunska literatura uredi
- Emery EC, Luiz AP, Wood JN (august 2016). "Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief". Expert Opinion on Therapeutic Targets. 20 (8): 975–83. doi:10.1517/14728222.2016.1162295. PMC 4950419. PMID 26941184.
Vanjski linkovi uredi
- SCN9A protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NCBI/NIH/UW entry on SCN9A-Related Inherited Erythromelalgia
- Q15858