ell-type kaalsyam chaanal

ell-type kaalsyam chaanal (dihydropyridine chaanal allengil dhp chaanal ennum ariyappedunnu) volteju-ashrita kaalsyam chaanalinte hye-volteju activated kudumbatthinte bhagamaanu.
"l" ennaal sajeevamaakkalinte dairkhyathe soochippikkunna deerghakaalathe soochippikkunnu. eee chaanalin naalu isophomukalundu cav1.1, cav1.2, cav1.3, cav1.4.
asthikoodam, minusamarnna, hridaya peshikalude eksaitteshan-kontraakshan couplingin adrenal courtexinte endocrine koshangalile aaldostiron sravathinum ell-type kaalsyam chaanalukal utharavaadikalaanu. avaa neuronukalilum kaanapedunnu, endocrine koshangalile ell-type kaalsyam chaanalukalude sahaayathode avaa neurohormonukaleyum neuro traansmittarukaleyum niyanthrikkunnu. jeane expression, mrna sthiratha, neuronal athijeevanam, ischemic-induced axonal parikk, synaptic falaprapti, mattu ayoon chaanalukalude sajeevamakkalum nirjeevamaakkalum ennivayil avaa oru punk vahikkunnathayi kaanapedunnu.
cardiac myosaittukalil, ell-type kaalsyam chaanal akathekku aaya + karant (icl) kadannupokukayum rhianodine risapttar 2 2 (kaalsyam-induced-kaalsyam-release) sajeevamaakkunnathiloode sarcoplasmic rettikulathil ninnu kaalsyam purathuvidunnathinu kaaranamaakukayum cheiyunnu. eee chaanalukalude phosphorylation kaalsyathilekkulla avayude praveshanakshamatha vardhippikkukayum athath cardiac mayosaittukalude churukkam vardhippikkukayum cheiyunnu.
ell-type kaalsyam chaanal blocker marunnukal hridayathodu (verapamil polulla phenylalkilamines) allengil rakthakkuzhalukalk (nephedipine polulla dihydropyridinukal) uyarnna aduppamundo ennathine aashrayich cardiac antiarithamics allengil antihypertensive aayi upayogikkunnu.
asthikooda peshikalil, tii-tubuleukalil sthithi cheiyunna ell-type kaalsyam chaanalukalude valare uyarnna saandrathayundu. peshikalude depolarisation valia gating pravaahangalkk kaaranamaakunnu, ennaal ionic pravaahangalude valare mandagathiyilulla sajeevamaakkal ippol vishadeekarikkunna kramarahithamaya kuranja kaalsyam fluxes. ekkaaranathaal, orotta aakshan pottensialil tii-tuble membraniloode cheriyatho allathatho aaya aaya + kadannupokunnu.
charithram.
1953ll pooll faattum bernard kaatsum crustasian peshikalil volteju gated kaalsyam chaanalukal kandethi. chaanalukal vyathyastha aaktiveshan voltejukalum kaalsyam contecting propertykalum pradarshippikkukayum angane uyarnna volteju activating chaanalukalaayum (echvie) kuranja volteju activating chaanalukalaayum (elva) verthirikkappedukayum cheythu. kooduthal pareekshanangalkk sesham, echvie chaanalukal 1,4-dihydropyridine (dhps) aayi thurakkumennu kandethi. dhps upayogichu, echvie chaanalukal chila tissuekalkk prathyekamaanennum vyathyasthamayi prathikarikkunnuvennum avar kandethi, ithu echvie chaanalukale ell-type, pii-type, enn-type enningane kooduthal tharamthirikkunnathilekku nayichu. ell-type kaalsyam chaanalukal pepttaid sequence cheythirunnathinaal 4 tharam ell-type kaalsyam chaanalukal undennu kandethithi α1s (asthikooda peshi), α1c (cardiac), α1d (thalachoril kaanapedunnu), α1f (rettinayil kaanapedunnu). 2000-ll, volteju gated kaalsyam chaanalukalile α1 sabyoonittukalil kooduthal gaveshanam nadatthiya sesham, ell-type kaalsyam chaanalukal kyaav 1 ennu vilikkunna oru puthiya namakaranam upayogichu, athinte subunitukale cav1.1, cav1.2, cav1.3, cav1.4 ennu vilikkunnu. kyaav 1 subunitukalekkurichu gaveshanam avayude ghadana, pravartthanam, farmaceutical aaplikkeshanukal ennivayekkurichu kooduthal velippeduthunnathu thudarunnu.
ghadana.
ell-type kaalsyam chaanalukalil 5 vyathyastha upavibhagangal adangiyirikkunnu, α1 (170-240 kda), α2 (150kda), δ (17-25 kda), β (50-78 kda), γ (32kda) upavibhagangal. α2, δ, β subunitukal α1 subunitumaayi noonn-kovalanti boond cheythirikkunnu, koodaathe ayoon trafficing α1 sabyoonittinte biophysical propertykalum modulate cheiyunnu. α2, δ subunitukal extra sellular speysilum β, γ subunitukal cytosolic speysilumaanu sthithi cheiyunnathu.
aii-aivi domainukal ennariyappedunna naalu transmembran pradeshangalulla oru hettero tetrameraanu α1 subunit, avaa plasmaye aarr thavana α-helixukal aayi kadakkunnu, avaye s0-s6 ennu vilikkunnu (s0 umm s1 umm orumichu membran orikkal kadakkunnu). mothatthil α1 subunitil volteju sensing domaine, kandakshan pore, gating upakaranam enniva adangiyirikkunnu. mikka volteju-gated ayoon chaanalukaleyum pole, α-subunit 4 subunitukal chernnathaanu. oro sabyoonittum roopappedunnathu membron (nambar cheytha s1-s6) kadakkunna 6 alfa-heelikkal, transmembran domainukalaanu. domainukalaanu subunitukalaanu volteju sensor nirmmikkunnath, athesamayam linkarukaliloode-ezz5 subunitukalaanu selectivity filter nirmmikkunnath. koshatthinte volteju manassilakkaan, manassilakkaan helisukalil niravadhi negatteevu charjju cheytha amino aasidukal adangiyirikkunnu, athesamayam helix helisukalil helisukalil linkarukaliloode helisukalumaayi bandhippikkunna pii-lupulla positteev charjju cheytha amino aasidukal adangiyirikkunnu. adangiyirikkunnu domainukalkku sesham, rund ef-hand motifukalum motifukalum, (sii1-2 oru pree-aiku domain domain aiku domain domain ulkkollunna aarr sii domainukalundu. enn-terminasil rund ef-hand motifukalum undu. sii-terminasinu enn-terminessinekkaal valare neelamulla cytosolic sthalathaanu enn, sii terminesukal.
chaanalinte pravartthanangal niyanthrikkunnathin β sabyoonittin naalu isophomukal (β1-β4) undennu ariyappedunnu, koodaathe β α1-binding pokkattile (eiii. bii. pii) cytosolile α1i, II linker vazhi α1-maayi bandhippichirikkunnu. oro isophomilum oru src homology 3 domain domain oru hook domain gadanayillaatha moonnu pradeshangalum upayogichu verthirikkunna oru gwaanilettu-kinez polulla domain (jike) adangiyirikkunnu.
α2, δ subunitukal disulfide bondukalaal (chilappol α2δ subunit ennariyappedunnu) orumichu bandhippikkukayum α1-maayi samvadikkukayum cheiyunnu. avaykku α2δ-1 muthal α2δ-2 vare ariyappedunna naalu isophomukalundu, koodaathe oru voonn willebrand a (vwa) domain oru kaashe domain adangiyirikkunnu. α2 pradesham extra sellular spaceilaanu, δ pradesham sell membranilaanu, glycosylphosphatilistine (gpi) aankar upayogichu nankooramidunnathaayi kaanapedunnu.
γ sabyoonittin ettu isophomukalundu (γ1-γ8), ithu α1 subunitumaayi bandhippichirikkunnu, ithu cav1.1, cav1.2 chaanalukalile peshi koshangalil maathrame kaanappedunnulloo. γ subunitinekkurichu kooduthalonnum ariyillengilum ithu hydrophobic shakthikalile edapedalukalumaayi bandhappettirikkunnu.
samvidaanam.
ell-type kaalsyam chaanalukalile sushirangalude thurakkal α1 subunitilaanu nadakkunnathu. membran depolarise cheyyumbol, helix helix helix, linkarukaliloode linkarukaliloode linkarukaliloode, ezz5 helixukalude cytoplasmic attangalilekku neengunnu. ithu α1 sabyoonittile s6 helisukalude aantharika vasham roopeekarikkunna aaktiveshan gettu thurakkunnu.
ell-type kaalsyam chaanalukalude autoinhibision ettavum pradhana maarggam/kyaam complexes aanu. sushirangal thurakkukayum kaalsyatthinte ozhukk undaakkukayum cheyyumbol, kaalsyam kalmodulinumaayi bandhippikkukayum thudarnnu aduthulla ef-hand motifukale bandhippikkunna looppumaayi samvadikkukayum ef-hand motifil oru roopabhedam varuthukayum cheiyunnu, athinaal ithu sushiravumaayi samvadikkukayum chanalil pettennulla thadassam srishtikkukayum cheiyunnu. sushirangalum iii. eph-hand evide, engane edapedunnu ennathinekkurichu ippozhum charcha nadakkunnundu. / kyaam complexile hydrophobic pokkattukal "aarometik ankerukal" ennariyappedunna ikyu domaininte moonnu vibhagangalumaayi bandhippikkum. / kyaam complexinu ell-type kaalsyam chaanalukalumayi uyarnna aduppamundu, ithu koshatthil kuranja alavil kaalsyam ullappol polum athu thadayaan anuvadikkunnu. koshatthinte punardhruveekaranam moolam sushirangal oduvil adayukayum athu adanja roopathil sthaapikkunnathinu chanalil oru roopabhedam varuthukayum cheiyunnu.
inhibition modulation.
ell-type kaalsyam chaanalinte ettavum amgeekarikkappetta savisheshathakalilonn 1,4-dihydropyridinukalodul (dhps) savisheshamaaya samvedanakshamathayaanu. mattu volteju gated kaalsyam chaanalukalil ninnu vyathyasthamayi, ell-type kaalsyam chaanalukal Â-ctx (jiviya), Â-aga (aivaa) inhibittari marunnukale prathirodhikkunnu.
nannayi nireekshikkappedunna modulationte oru roopam badal spliesing moolamaanu. sii-terminal modulator (sii. tii. emm) aanu badal spliesingil ninnulla moduleshante oru saadhaarana roopam. ithinu dcrd ennu vilikkunna sii-terminalil positteev charjju cheytha α-helix pcrd ennu vilikkunna ikyu motifinu (kyaam interaakshan saitt) thottupinnaale negatteevu charjju cheytha helix undu. rund helikkukalkkum ooppan-stettu probability kuraykkaanum kaalsyam ashrita inhibition (cdi) kuraykkaanum kyaam-maayi mathsaraadhishtithamaayi bandhippikkunna oru ghadana roopeekarikkaan kazhiyum.
paalmittoyleshan, rna editting enniva kaaranam chanalukalkk vyathyastha gunangal nalkunnathinu vyathyastha isophomukal srishtikkunnathinaayi β sabyoonittukalil badal spliesing kaanapedunnu. β sabyoonittile moduleshante mattu roopangalil sabyoonittinte expression vardhippikkukayo kuraykkukayo cheyyuka ennathaanu. β subunitukal chaanalinte thuranna saadhyatha vardhippikkukayum plasma membranile pravartthanam vardhippikkukayum chaanalinte sarvvyaapithvathe ethirkkukayum cheiyunnathaanu ithinu kaaranam.
jii protein-cuppled resepterukalum adrenergic naadeevyavasthayum ell-type kaalsyam chaanalukal modulate cheiyunnu. jii protein-cuppled resepterukal cascade sajeevamaakkunna protein kainas eiii (pka) kku eiii-kainas-ankering proteinukal (accaps) upayogichu oru signalling complexes roopeekarichathinu sesham chaanaliloode kaalsyam karant vardhippikkunnathinum ooppan-stettu probability vardhippikkunnathinum thwarithappeduthiya veendedukkal kaalayalavinum phosphorilettu ell-type kaalsyam chanalukalkk kazhiyum. jii protein-cuppled resepterukalil ninnulla activated phospholipase sii (pii. ell. sii) kku polyphosphoinositude thakarth chaanalukalile kaalsyam karant <aii. dii. 1> kuraykkaan kazhiyum.
chaanalukalude sajeevamaakkal vardhippikkunnathinaayi β-adrenergic risapttar uthejippikkumbol sii-terminal sakalam pilarthunnathiloode ell-type kaalsyam chaanalukale adrenergic nadiviewham modulate cheiyunnathaayi kaanapedunnu.

