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7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
1/43
Vlptlcjlr :7, :7>6
Vlf`hm Khtlrhntk`hni R`resd`p `h FNMNVKI
Cnre Hlis`h
Jurikhbt`h, _lrc`ht
C`uht Cnhsoklim \hkvlrskty `o _lrc`ht
W`tnsskuc fdnhhlis, Hlur`vnsfuinr F`upikhb, FNMNVKI
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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"Nhm wdnt pdyskfknhs sny nj`ut mkslnsl ks nppikfnjil dlrl1 tdnt
nt tdl jlbkhhkhb n mkslnsl ks lnsy t` furl jut mkookfuit t`
mknbh`sl5 jut ns tkcl pnssls, h`t dnvkhb jllh trlntlm `rrlf`bhkzlm nt tdl `utslt, kt jlf`cls lnsy t` mknbh`sl jut
mkookfuit t` furl. ]dl sncl tdkhb `ffurs kh noonkrs `o stntl5 o`r jy
rlf`bhkzkhb or`c nonr tdl mkslnsls tdnt nrl sprlnmkhb kh tdl
stntl (wdkfd ks n bkot bkvlh `hiy t` n prumlht ruilr), tdly fnh jl
furlm qukfeiy5 jut wdlh tdly nrl h`t rlf`bhkzlm nhm nrl ilot t`
br`w t` tdl lxtlht tdnt lvlry`hl rlf`bhkzls tdlc, tdlrl ks h`
i`hblr nhy furl.
Hkff`i` Cnfdknvliik(nen Onjrkfl Mnjlrtrnhm)
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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O`hmntk`h Ilmufq ]rnhsntinhtkf Hltw`re `o Lxfliilhfl
Wntd`blhlsks `o Vcnii _lssli Mkslnsl `o tdl Jrnkh
Lur`plnh F``rmkhnt`r
Nhhl A@\]LI (Ornhfl)
KHVLZC Zlslnrfd Mkrlft`r
Blhltkfs `o _nsfuinr Mkslnsls Inj`rnt`ry-
KHVLZC
\hkvlrskty Wnrks2-Mlhks Mkmlr`t
>7 nvlhul ml _lrmuh, 27 Wnrks, Ornhfl
nhhl.a`utliGuhkv-pnrks-mkmlr`t.or
Wd`hl1 7>
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Jrnkh survkvni
Nut`rlbuintk`h1 Cnkhtnkhkhb f`hstnhtji``m oi`w kh rlsp`hsl t` ji``m
prlssurl oiuftuntk`hs.
Hlur`vnsfuinr f`upikhb1 Zlbk`hnif`upikhb `o flrljrni ji``m oi`w t` tdl
cltnj`ikf mlcnhm `o hlur`hs.
]dl jrnkh p`sslssls khtrkhskf clfdnhkscs jy wdkfd ktsvnsfuinr suppiy fnh jl vnrklm i`fniiy kh f`rrlsp`hmlhfl
wktd i`fni vnrkntk`hs `o ouhftk`hni nftkvkty (Z`y nhm
Vdlrrkhbt`h, >4;7)
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Kcpikfntk`hs `o hlur`vnsfuinr
f`upikhb
Ouhftk`hni jrnkh kcnbkhb jy c`hkt`rkhb
i`fni flrljrni ji``m oi`w wktd oCZK.
\hmlrstnhmkhb `o jrnkh mkslnsls tdnt nrl
nss`fkntlm wktd hlur`vnsfuinr
mysouhftk`h, khfiumkhb str`el, Nizdlkclrs,
vnsfuinr mlclhtkn, dyplrtlhsk`h.
C`muintk`h `o hlurni pr`flsskhb.
]d H i \ k
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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]dl Hlur`vnsfuinr \hkt
Nrtlrk`ils kh tdl jrnkh nrl lhfnslm jy nstr`fytkf
pr`flssls
Knmlf`in,
Hnturl
Zlvklws,
Hlur`sfklhfl,
:77=
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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]dl Hlur`vnsfuinr \hkt
>7 c
Nstr`fytl
lhmollt
Vc``td cusfil
WlrkfytlLhm`tdlikuc
Hlur`hs
Nstr`fytl lhmollt f`cpiltliy lhfnsl tdl khtrnflrljrni vnsfuinturl nhm nrl tdus
uhkquliy p`sktk`hlm t` mlikvlr skbhnikhb c`ilfuinr t` tdl uhmlriykhb sc``td
cusfil
Lhm`tdlikni fliis ikhl tdl iuclh `o tdl nrtlrk`ils, nhm f`ccuhkfntl ji``m-j`rhlskbhnis t` sc``td cusfil t` noolft t`hl
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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N pinstkf lcuisk`h wns khalftlm kht` tdl jrnkh vlsslis, nhm
jrnkh pnrlhfdycni tkssul wns mkss`ivlm
(Qi`e`vkf & Npuzz`, >;;45 Ikppkhf`tt Rkiikncs & Rkiekhs)
Hlur`vnsfuinr f`upikhb
Muhh, E. C. nhm C. ]. Hlis`h (:7>7). "W`tnsskuc Fdnhhlis nhm
Hlur`vnsfuinr F`upikhb." Fkrfuintk`h A`urhni 2=(=)1 ?74-?>?
Ilvli `o nstr`fytkf lhmo``tFn:+ mltlrckhls wdltdlr nh
nmanflht nrtlrk`il mkintls `r
f`hstrkfts mlplhmkhb
`h plrkvnsfuinr E+.
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Khdlrktlm scnii vlssli mkslnsl fnuskhb
str`el nhm sujf`rtkfni vnsfuinr mlclhtkntdnt stnrts kh lnriy nmuitd``m nhmpr`brlssls `vlr tkcl.
FNMNVKI
Fnuslm jy cutntk`hs kh H@]FD6 blhl
Or`c Fdnjrknt D lt ni. Inhflt Hlur i. :77; Aui54(2)1?=6-7 nhm >>
rlqukrlm o`r ikbnhm jkmkhb
Clfdnhkscs ikhekhb H`tfd6 cutntk`h t` vnsfuinr kcpnkrclht rlcnkh lhkbcntkf
Flrljrni
Nut`s`cni
M`ckhnht
Nrtlrk`pntdy wktd
Vujf`rtkfni
Khonrfts &
Iluf`lhflpdni`pntdy
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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]dl c`usl c`mli
I`ss `o H`tfd6 fnusls strufturni nhm ouhftk`hni nitlrntk`hs `o scnii nrtlrkls, jut m`ls
h`t fnusl FNMNVKI pntd`i`by. (Iku lt ni Fkrf Zls :7>7)
Nhhl A`utli nhm f`w`relrs uslm n W>-mlrkvlm nrtkokfkni fdr`c`s`cl-jnslmtrnhsblhlsks t` `vlrlxprlss H`tfd6 kh nh lhm`blh`us-ikel lxprlssk`h pnttlrh. Ikhl
>:; `vlrlxprlssls (x=) rnt wkim-typl H`tfd6 blhl, nhm ikhl 44 `vlrlxprlssls (x=) n
FNMNVKI o`rc H`tfd6Z>?;F.
H`h-]b ]bH`tfd6R] ]bH`tfd6Z>?;F
H`tfd6
H`tfd6
H`tfd6
H`tfd6H`tfd6
H`tfd6
H`tfd6H`tfd6
H`tfd6 H`tfd6
H`tfd6
H`tfd6
H`tfd6Z>?;F H`tfd6
H`tfd6
H`tfd6Z>?;FH`tfd6Z>?;F
H`tfd6Z>?;F
H`tfd6Z>?;FH`tfd6Z>?;F
H`tfd6Z>?;F
H`tfd6Z>?;F
A`utli N lt ni. A Fikh Khvlst. (:7>7) >:7(:)1=66-=
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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[`uhb ]bZ>?;F (7) >:7(:)1=66-=
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Z`k Fn:+ c`vkls `hiy
Wnrlhfdycni nrtlrk`il wktd pnrlht ckmmil flrljrni nrtlry
(Zlm, nqunp`rkh = (nstr`fytl) stnkhkhb)
(Or`c Dnhhnd lt ni., AFJOC, :7>>)
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Clcjrnhl p`tlhtkni nhm mkncltlr clnsurlclhts `o prlssurkzlm
pnrlhfdycni nrtlrk`il
Lmbl mltlftk`hsystlc
Wrlssurkzlm
WN (=7 cc Db)
ckfr`lilftr`ml
Fnhhuin
C`hkt`r]kl
Clcjrnhl p`tlhtkni
(c_)
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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\prlbuintk`h `o p`tnsskuc
fdnhhli nftkvkty t` `pp`slkhfrlnsls kh khtrnvnsfuinr
prlssurl
`hl wny NH@_N
FNMNVKI pnrlhfdycni nrtlrk`ils f`hstrkft ilss t`
khtrnvnsfuinr prlssurl
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Zlskstnhfl-skzlm clslhtlrkf nrtlrkls mkspiny
h`rcni cy`blhkf t`hl
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K`h fdnhhli f`htr`i `o sc``td cusfil clcjrnhl p`tlhtkni
nhm khtrnfliiuinr fnifkuc
Ev1 _`itnbl-mlplhmlht p`tnsskuc fdnhhli.
JEFn1 Inrbl-f`hmuftnhfl, fnifkuc-slhsktkvl p`tnsskuc fdnhhli.
Ekr1 Vtr`hb khwnrm rlftkoklr p`tnsskuc fdnhhli. Nftkvntlm jy lxtlrhni E+ nhm clcjrnhl
p`tlhtkni dyplrp`inrkzntk`h.KEFn1 Khtlrclmkntl f`hmuftnhfl, fnifkuc-nftkvntlm p`tnsskuc fdnhhli.
VEFn1 Vcnii f`hmuftnhfl, fnifkuc-nftkvntlm p`tnsskuc fdnhhli.
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Lxtlrhni E+` ks n p`tlht nhm rnpkm vns`mkint`r nhm f`hstrkft`r
`o prlssurkzlm (47 cc Db) flrljrni nrtlrkls
Eh`t lt ni., A. Wdysk`i., >;;4
>> >?:>
Hks`imkpkhl(>7 hC)
Lxtlrhni UE S(cC)
+
:? 6>6? =>
4>?>
677
Nstr`fytkf
Lhmo``t Fnifkuc
JE
Wlrkvnsfuinr E+
Mkintk`h
9:7 cC
F`hstrkftk`h
8:7 cC
Fnifkuc fdnhhli khdkjkt`r
Mkintk`h t`Ekr:.> nftkvntk`h
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Clcjrnhl p`tlhtkni `o vnsfuinr sc``td cusfil mltlrckhls
nrtlrkni mkncltlr nhm dlhfl ji``m oi`w
(Lxtlrhni E+ rlbuintls clcjrnhl p`tlhtkni)
Eh`t & Hlis`h, A Wdysk`i >;;4
Fnifkuc fdnhhlis khdkjktlm
Mlntd
Ikol
Mlntd
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Mkintk`h nhm f`hstrkftk`h t` lilvntk`h `o UE+S7 or`c 6 t` ?7
cC nrl uhnoolftlm kh FNMNVKI
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Clcjrnhl p`tlhtkni `o nrtlrk`inr sc``td cusfil or`c
FNMNVKI ckfl ks dyplrp`inrkzlm nt =7 cc Db
H`h-]b
]bF`htr`i
]bZ>?;F
_c (c_)
-6=
7.?
-6.?
-==.:
>.=
=7
cc Db
-
-
>7
cc Db
`hl wny NH@_N
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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K`h fdnhhli f`htr`i `o sc``td cusfil clcjrnhl p`tlhtkni
nhm khtrnfliiuinr fnifkuc
Ev1 _`itnbl-mlplhmlht p`tnsskuc fdnhhli.
JEFn1 Inrbl-f`hmuftnhfl, fnifkuc-slhsktkvl p`tnsskuc fdnhhli.
Ekr1 Vtr`hb khwnrm rlftkoklr p`tnsskuc fdnhhli. Nftkvntlm jy lxtlrhni E+ nhm clcjrnhl
p`tlhtkni dyplrp`inrkzntk`h.KEFn1 Khtlrclmkntl f`hmuftnhfl, fnifkuc-nftkvntlm p`tnsskuc fdnhhli.
VEFn1 Vcnii f`hmuftnhfl, fnifkuc-nftkvntlm p`tnsskuc fdnhhli.
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Ncpd`tlrkfkh J
p`rl
Mkrlft clnsurlclhts `o p`tnsskuc fdnhhli nftkvkty uskhb
tdl pntfd fincp tlfdhkqul
Nmnptlm or`c dttp1//pntfd-fincp.kho`/tlfdhkquls/tlfdhkquls.dtc
-47 c_ -27 c_
+?7 c_
-=7 c_
Lxplrkclht f`hmuftlm kh tdl njslhfl `o
Fn:+, nhm kh prlslhfl `o JE ji`felr
pnxkiikhl
@jalftkvl1 f`cpnrl furrlhts or`c
ks`intlm nrtlrk`inr sc``td cusfil flii
likfktlm jy v`itnbl puisls or`c
-27 c_ t` +?7 c_.
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Furrlht mlhsktkls nrl mkoolrlht or`c -67 c_ t` ?7 c_
Furrlht mlhskty `o v`itnbl-mlplhmlht E+ fdnhhlis ks brlntlr kh FNMNVKI
(flii clcjrnhl suronfl nrln ks uhnoolftlm)
`hl wny NH@_N
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Wrlssurl-khmuflm f`hstrkftk`hs nrl uhnitlrlm nt i`wlr prlssurls (967 cc Db)
jut cy`blhkf t`hl ks mlfrlnslm nt pdysk`i`bkfni prlssurls kh j`td pkni nrtlrklsnhm pnrlhfdycni nrtlrk`ils (WNs) or`c FNMNVKI ckfl.
Kcpikfntk`h1 Wrlssurl-mlplhmlht clfdnhksc ks nitlrlm kh FNMNVKI.
D`wlvlr, f`htrnftkil ouhftk`h ks prlslrvlm wktd mkncltlr fdnhbls t`
p`tnsskuc jlkhb uhnitlrlm.
WNs or`c FNMNVKI ckfl sd`w n c`rl dyplrp`inrkzlm clcjrnhl p`tlhtkni nt
=7 cc Db. JE, KE, VE fdnhhlis nhm lH@V ouhftk`h m` h`t npplnr mkoolrlht kh FNMNVKI
c`usl.
_`itnbl-mlplhmlht p`tnsskuc (Ev) fdnhhli furrlht mlhskty ks lilvntlm kh
flrljr`vnsfuinr sc``td cusfil fliis or`c FNMNVKI ckfl.
Wrlssurl _c
mlp`inrkzntk`hUFn:+Sk Mkncltlr FJO
Ev
JE, LF ouhftk`h (KE, VE, lH@V)
Flrljrni Ji``m Oi`w nut`rlbuintk`h ks nitlrlm kh
FNMNVKI
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Vujnrnfdh`km dlc`rrdnbl ji``m khfrlnsls prlssurl-khmuflm f`hstrkftk`hs
tdr`ubd m`whrlbuintk`h `o v`itnbl-mlplhmlht p`tnsskuc fdnhhlis
Cnsny` E`kml
Nmrknh J`hlv
Bl`rbl Rliicnh
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E`kml lt ni.NAW:772Ksdkbur` lt ni. Fkrf Zls :77?
Ev fdnhhli trnookfekhb ks rlbuintlm jy cltnii`pr`tlkhnsl (CCW) tdr`ubd
dlpnrkh jkhmkhb lpkmlrcni br`wtd onft`r ikel br`wtd onft`r (LBOZ)
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Dlpnrkh-jkhmkhb Lpkmlrcni Br`wtd Onft`r (DJ-LBO)
khmufls Ev furrlht supprlssk`h
E`kml lt ni.NAW Dlnrt Fkrf Wdysk`i. :772 Vlp5:;6(6)1D>2
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Wnkrlm ]-tlst
DJ-LBO rlst`rls cy`blhkf rlsp`hsl kh flrljrni
nrtlrkls or`c FNMNVKI c`usl
F
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Or`c E`kml :772
Lxflss `o H`tfd6LFM njh`rcniiy stnjkikzls ]KCW6
(B@C o`rcntk`h), wdkfd khfrlnsls Ev fdnhhlis nt tdl
clcjrnhl t` `pp`sl prlssurl-khmuflm f`hstrkftk`h
sdlmmkhb
H`tfd6LFM
H`tfd6KFMBlhl lxprlssk`h (Ev >.
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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]w` nppr`nfdls t` rlst`rl cy`blhkf t`hl kh
FNMNVKI
Blhltkf rlmuftk`h `o ]KCW-6
rlst`rls cy`blhkf t`hl kh
p`stlrk`r flrljrni nrtlrkls(kh Wnrks)
Wdnrcnf`i`bkf nftkvntk`h `o LBOZ
rlst`rls cy`blhkf t`hl kh
pnrlhfdycni nrtlrk`ils(kh Jurikhbt`h)
N clfdnhksc jy wdkfd H`tfd6 cutntk`h ilnms t` n vnsfuinr
kcpnkrclht
Wilk`tr`pkf loolft `o H`tfd6Z>?;F vkn
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I`fni ji``m oi`w
Nstr`fytl lhmo``t
Vc``td cusfil
Lhm`tdlikuc
JE
E+E+E+
F`hstrkftk`h
Mkintk`h
E+
Ekr
LC
WIN:NN
Wr`stnbinhmkhs/
pr`stnfyfikh
Mkintk`h
I`fni ji``m oi`w
++
-
:7-DL]L
LL]
Fn:+ wnvl
Hlur`hni nftkvkty
Fnrt``h or`c Br` Eiktbnnrm W`vislh
Wilk`tr`pkf loolft `o H`tfd6Z>?;F vkn
B@C0
B@C o`rcntk`h
B i @ k dkik C t k i (B@C) m t t m
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> c
Brnhuinr @sck`pdkikf Cntlrkni (B@C) nrl mltlftlm
jltwllh sc``td cusfil fliis nhm nstr`fytkf lhmo``t
Or`c Nhhl A`utli
CL]D@MV
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Jrnkh sikfls i`nmlm wktd
Oiu`-=.NC
. LOV, Fn:+ uhfnbkhb
>. F`r`hni jrnkh sikfls or`c hl`hntni rnts W; (>:< hC )
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Hlur`vnsfuinr f`upikhb1 Lilvntk`h `o nstr`fytkf lhmo``t
Fn:+ fnusls vns`mkintk`h
LOV 3 Lilftrkfni Oklim Vtkcuintk`h
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LOV-khmuflm mkintk`h ks rlmuflm kh
FNMNVKI ckfl
:
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LOV-khmuflm Fn:+ khfrlnsl kh nstr`fytkf
lhmo``t ks rlmuflm kh FNMNVKI ckfl
Onstlr UFn:+S mlfny kh lhmollt or`c
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E 7.76:>
Dnio Ikol >:.?> 4.>; 2.
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R`rekhb Dyp`tdlsks1
Lnriy f`hslqulhfl `o FNMNVKI ks
uprlbuintk`h `o Ev >.< lxprlssk`h nhm nftkvktywdkfd ilnms t` f`cpr`ckslm nut`rlbuintk`h.
Lilvntk`h `o tdl cltnii`pr`tlkhnsl ]KCW6 kh
B@C ilnms t` nh khfrlnsl kh suronfl
lxprlssk`h `o Ev fdnhhlis.
Mlfrlnslm cy`blhkf t`hl w`uim mkckhksd
vns`mkint`r fnpnfkty, nhm tdlrljy
hlur`vnsfuinr f`upikhb. FNMNVKI ikeliy nttlhuntls nstr`fytl lhmo``t
fnifkuc skbhnikhb t` mlflnsl hlur`vnsfuinr
f`upikhb.
N e i m t
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Nfeh`wilmblclhts
Ouhmkhb1Nclrkfnh Dlnrt Nss`fkntk`h, ]`tcnhClmkfni Zlslnrfd ]rust, Iuhmjlfe O`uhmntk`h
Hntk`hni Khstktutl `o Dlnitd, O`hmntk`h Ilmufq
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A`hntdnh Ilm`ux
Nmrknh J`hlv
Onjrkfl Mnjlrtrnhm
Nhhl A`utli
Fdrkstli Erkbnnrm
Fnrclh Fnp`hl
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Clrfk! Mnhel! ]dnhe [`u!
7/29/2019 Mark Nelson - Potassium channels and neurovascular coupling
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Clrfk! Mnhel! ]dnhe [`u!
]dl Inj
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