Población en hogares por sexo de los integrantes y tipo de hogar 2005

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2.12 CALCIUl\1 IIOl\1EOSTASIS

The divalent calcium cation Ca ¹ has a unique posi11on nmong ccllulnr ions 1n higher organisms In its insoluble form. Ca ² ploys unpor1ant roles such as acting as o membrane stab11J1cr. cofactor for proteins. electric ch.irge earner and dtlTus1ble 1ntracellulor messenger (Campbell. 19113, Comfoll. 1987) 'The tollll Ca ^{2 '} concenLrallon 1n e.·dracellulnr b1olog1c nu1ds

such as blood serum ranges from I 6 to 2mm (of\\ lucb opproX11Mtely 50')o is bound to protem and olhcr constituents (Kass, 1999) Within cells, ea ^{2 •} 1n bound pnmanl) to phosphohp1ds.

proton and nucleic ocid or sequestered 1n organelles and onl) 0 I')., of the tollll cellular Ca ² content 1s found free 1n the cytosol Consequently: the cylosohc fn::o conccntrollon ((Co ² I) 1s IJ:pt around O 1 µm and onl) the mmute frncuon of the ^101Jll ccllulnr Ca ^{2 LS} O\IUlablc for perfonrung functions such as diarge earner or di1TUS1blc messenger

c,i1' ,s a un1,em,J ,nll'DGCllulor messenger lh:11 poruopa1cs 1n numerous b1olosical processes from neural r�ullltion to mu.sclc a>ntrllCUOn and from gene expression ¹⁰ ccU gro,,th and

dCOl!h (Oomdgp et al 2000) llus 1ncn:d1blc vcrsallhl) n�1u11cs lhnl 1n1rncellulor Co ¹ conccntn1uon be 11ghll) rcgullllcd, IO = coord,nonon amone 1hc mult1plc proces-;es

in\oh·,n1i c,r th.u underlie no� cell func11orung. Thus 1m1"11CC1lular en�· homcostasis 1s 0 prcn:,qws11c for a he:illh) cell life. Impair rq.'lll11uon of Co ¹ c:onccnlllllJOn anm lctld 10 cell dy1func11on such as occur ,n life thtc::i1Cn1n9 d�scs

' }•

J'or �JIIC. a lfWlSICJlt 1nuc:a:.o of (.a C:Onccnl,-llOfl IS required IO IRtllblC COOll"DCIIOI\ or

muKlt' cc:lls, 1Nlh1hl> ^ID dc•atc Ca conccnlnllJOn lO lbc lc,c:1 or rol101-.n111n C'.\c111111on ^ti a ma.,or plllho£'Cn•c: mcc:h&tumt 1n IIClft wlu11, (Gurne, �, 11/, :ZOOI) In contnut, t".COII\ c

ctc:, Dllon of ,ounc ^C&

^' QJllCcnll"lllOn 11 ddetmou, to almost all cell I) pc, and c:in t,e n:.socuucJ ... uh alhct ^n«101Jc or ap,ptohe ull Jc::llh (Trurr., and lkrc.,c:t..,, 1•1:>i)

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lntraccllulnr Co ² ' homcostas1s ^is nl"'n)-s important for a healthy a:11 life. Therefore. a prec1Se understanding of 1nuacellulnr Cll ^{2 '} homeosras1s 1s tantamount not only to understanding the

nnlure but nJso the development of novel thcrupu:s for treaung diseases.

The resting intracellular calcium conccntrn11on or 11Cllvity is mrunllllncd 1n the range of I 0-1 OOnM whereas the ex'trncellular Co ^{2 '} concentrauon is 1n lhe mM range (Abdcl1lah, 200-t) To m:unlain this lo\v range ea ^l • 1s ocU\ely pumpod from cytosol to lhe c.,trnccllular space and 1n10 lhe cndoplasrruc reoculurn {ER) and someun,es 1n ihe muochondnn. TI1e l11gh clcctrochcm1cal gradient nllo\\'S rapid nse 1n local 1ntrucellular Co ² concentration onen referred to os events \\h1ch may tnkc pince O\cr the m1lhsccond Limcsc;alc and \\hich mn) easily rc:ich the µm levels This s11W11Jon oncn wcs bccnuse the plasma mcmbllllle hos ^\CC)

hmited and ,ery carefully controlled Co ² ' pcm1c:ibil1t) In I.he presence of n large Co ² peTTI1C3b1hty �,II result 1n s1gruliCllfll ^S\\10SS 1n the 1nlJ'UCcllular conccntrnt1on of Co ² and

\\Ould thus efTioentl) 1n0uence the mocful31JOO ofCA ^{2 ' targets} (CornfolJ, 19')1}

Dunng c,oluuon. ccllJ ha,c dC\cloped mnny soph1s11ca1cd and uniquely 1a1lorcd systems 1n order ¹⁰ effect efficient and fmt spUto-tcmponil dt:ingcs 1n 1nlfllCCllulnr Co' concentn111on (Abdehlah, 2004)

'Inc precue reguhwon of Ca ^{1 '} homco,tas,s ,n ccllll 1s o result or the concmcd l\mc.uorunl.' or trwuponc:n locauxt III the pla.1nQ mc1nbranc and l)'llcmi, opcnat1ng in ecll or�cllcs I c cndo­

s:ucoplmmic reticulum. m11oc:hondrua. nudeus and calc,um bonding protons

l;IJ Kl-Cl 1.A'OON OJI 1/\ifR.ACt:l.l,UI..AR Ca ¹ CONC•/\,TilATIO"I IN .\1M1�fAJ IAN Ct'l,14',

In both t:.'Cllllhlc 1111d non-OC1tablc «ll1 calc:1um ^lllffl efllrr lhrou(1l calc;ium ch.:uincl,. ,,tuc.h

11 c molecul&1 p;rc:s ⁱⁿ the mnnbJD'IC llw Dllo"'� larne numbl-n or ^Ca

^{• 1on11 11 010,0} do"n the conccnUllllOO ,:,11,hcna udD lhc a-II CC•oroh & Pcnnnlol\, 19''11 In C\.:llahlo c-cU, UNIVERSITY

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cnlc1um cho.nnels open 1n response to the acllon polcnllal, o ^l'C\ crsal m the nonnnl ,oltoge gradient across the membrane. An action polentJal 1s tnggered \\hen o messenger molecule

(usually a ncurotransm1tter) binds 10 a receptor ol the surface of the cell causing on 1ru11ol dcpolnnmllon, or change ta the ,·oltoge grndicnt.

Voltage scns11Jvc sodium channels 1n the membrane then open :1dmi1ong posni,ely charged sodium ions ^into I.he cell TI1e annu� causes the charge 11151de lhe membrane 10 chllngo from

ncgauvc 10 pos11Jvc.

Calcium channels, \\h1ch ^Dl'C normnlly closed. ore sensiu,-e to the mcmbrnnc po1cn!Jnls. The) begin 10 open as the po1enual nses above -30m.ilh,·01ts, at o po1enual of +30nullivolts; about 70 percent of celb calcium chnnncls nrc open. 'The ncllon potcnool pcal..s. at about , 40 nulh,ohs. At lh:11 po1n1 other ionic events {1ncludJng on o,·crno,\ of potassium ions) return the mcmbr:ine potenual 10 -90 rrulh,oll and the 1nOu., of cnlc1um ends. The voltage scns1tn c:

calcium chnnncls rcnwn open for onl) obout ^II nulh second, d:unng ,vtucb they odnut nboul 3.000 cnlc1um ions. Cl,'Cll \\hen lhe membrnnc po1ent1nl ^IS at us highest. the calcium chMnels 1n ^O cells mcmbrunc ore c:onunuall) opcrung and dos1n1? ,,uh 10,. of them orerunr al a ii" en insunl nus pCl'tctWltc ^a111 ,rc,cmc s11,vuficnnll) under the tnOucncc of C)chc oderunc monophosp.ihtc (c,V,,1P) �1P \\h1ch as made Ill the plllSffl:I nlCfflbmne ^\\hen hormones bind

to the cell surface rc:ccptors. ecuv111Jn11 tho c:rtl)fflC that phosphor) hues tho caJc1um cronncls Non c::u:itable cclb do not C'\pencncc acuon po1ent1als, their calcium channrl, cnnnoi be con1tollcd tr, ,olua,,:. In . ¹¹ uch odls, c:alc,um ch:annc:Js m:iy ^JUI} open pcmunen1ly or Iha mn\ .

bo rqiullllcd b) cAMI' -..Inch could pu.:&lly open� clasc lhrm. In t>llhcr ^CMc. the numb..'I of cJunncls or lhor c:alc,um conJua.:incr -..oulJ ric,c,J to be ,nwl 10 prc:1C11t l31i:c 1nt1u,n of c:alciunt To a,oiJ being ll<MxlcJ b, ^C4' r,0111 the c,trau:lful.at nulic:u cells h.,, ^{0 acqwr,'1}

during C\Oluuon a,oph1suc:atcJ trampnn rncdWIHl'nl lhal twl!'lulf) control acccu of(',11 ^1• Intl•

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the interior of a cell ncross the plasma membrane and rcd1S1nbution of Ca ² from the cytosol into 1ntracellular organelles (Carafoh, 1987, Tsicn and Tsien, 1990, Clnpham, 1995)

2.13.1 TllE Na•1ca ⁱ • EXCIIANGER

The transporter protein is pnruculnrly nbundJJJ1t C'<Cllnble cells; nerve and muscle cells, \Vluch repeatedly expencncc rapid influxes of cnJcum 10 response to electricnl impulses The sod,u.m - calcium exchanger \�h,ch ^\\'OS first d1SCOvercd 1n sqwd heart muscle and ncncs docs not

ccnenue the energy for cnlc1um trnnSpon independently unhl..e the cnlc1um pumping ATPose.

The exchorlger denvcs some of the energy needed to ^dri\C cnlc,um out of lhc cell from the concentmuon gradient or sodium It hns been c:stnbhshod bo\\"C\er lhnt three sodium ions 1010 the cell for every cnlc1um ,on thn1 1s exported Tins charge 1mbnlancc enables the transport process 10 tap the cic,8)· embodied m llic membrane potcnulll the gradient of \Oltnge across the membrnne of o.n-e.'<C.11llble cells In the rcsung slllle or the cell; the ,.ns,de of the mcmbn:u,a has o negnt1\e charge or 90 nulllvolts In effect. lhc lrnnSpOrt process allo,\'S cluuga 10 Oo\\

do"n the grndicnt bcc:111sr tJw: net effect or o� cycle of the e,chM1,-er 1s ¹⁰ niove one pos1t1\e dlllrr.c into the cell, thus both chem1CD.1 1111d clcctncnl grnd1cnts dn\ c the c,clwlger The c;ipACII)' or the cw141li;et ,s high It 1s also documcn1cd 1h31 the sodium ailcaum C\Ch:ingcr :r.cnc:s ^m:11nJ) to rtm0\e bite qull/UJIIC:S or c::llaum from =Ulble cells follo\\ing ,11mul:it1on (c:arufoh & pem1s1on. 198S)

1.1-4 l"ifRAC't-l.1,l l..AR Ca

^' S£QUl-.:.!.TRA t ION UV 01\CANf:LLl::.S

1.1-'.111,, Sacro-fndopwmlc Rrtlntlun, (St:R)

The 1,X1o<ndoplMm1c n:uc:ulu,n ^i» 1hr mAJor tntl'llCdlulllf Ca'' i1torc 1n n1<»1 cell t) re, _th, 1

orp,c:Jlc ,, c,qu1p,P(d ..,,th •4>pl1t.s•t011eol cdluw l}Ylcms allo\\1111111 11, qutel..l ) hurfcr or dllll,p 1ru111cdlulat c:olawn n,... (<;alM '' .ii l'l')'I, A11oJ'11J111U rt"'· 2002), pinbohl) lO ^JllC\ ml <'.D'"

C)totoua1y uld 10 n:lasc < •· 1n refl(lfflO 10 J1traer1t c:\tncc-llulor Jllmuh r 11 ¹ IC'-Ufllal..c

•IIIO the p,;;1o-crldoplas,nic n:oa.lum from the mlt 11>1racclluus n1.11n, or t'\toitl:i.\in '" UNIVERSITY OF

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