magistrsko delo
Nina Šutar (Avtor), Aleš Fajmut (Mentor)

Povzetek

V magistrski nalogi je izdelan in analiziran model za simulacijo od kalcija (Ca2+) odvisnega razvoja sile v gladkih mišičnih celicah (GMC) arterij. Z modelom simuliramo vpliv povišane produkcije cikličnega gvanozin monofosfata (cGMP), ki v celici nastane kot posledica povišane ravni dušikovega oksida (NO) v endoteliju žil, na obliko signala Ca2+ v citoplazmi GMC. NO lahko nastaja v endotelijski plasti žilne stene kot posledica povišane strižne napetosti krvi na stene arterij. NO iz endotelijskih celic difundira v gladko mišičnino, kjer stimulira produkcijo cGMP. V magistrskem delu je glavna tema modeliranje vpliva koncentracije tega sekundarnega prenašalca na od Ca2+ odvisen razvoj sile v GMC. V modelu za kodacijo signala Ca2+ v citoplazmi GMC upoštevamo vpliv molekule cGMP na od kalcija odvisne kanale za kalij (K+) (KCa) in klor (Cl-) (ClCa), izmenjevalce natrija (Na+) in kalcija (Ca2+) (NCX) in črpalke Na+ in K+ (Na/K). Poleg tega model vključuje še prehajanje Ca2+ skozi napetostno odvisne kanale (VOCC), črpalke za Ca2+ v celični membrani (PMCA) in v sarkoplazemskem retikulumu (SR) (SERCA), kanale, ki so odvisni od inozitol trifosfata (IP3) in Ca2+ (ICICR). Model vključuje še pasivno prehajanje vseh ionov, t.j. ionov Cl-, Na+, K+ in Ca2+ preko membrane. Z električnimi tokovi teh ionov je pogojena tudi membranska napetost. V modelu upoštevamo še vezavo Ca2+ na proteine v SR in v citoplazmi. Razvoj sile modeliramo s 4-stanjskim modelom interakcij med miozinom in aktinom, ki jih regulira aktivna oblika encima kinaze lahkih verig miozina (MLCK), ki je odvisna od Ca2+. Razvoj sile modeliramo v območju koncentracije cGMP med 0 in 10 x 10-3 mol/m3. Pri vrednosti [cGMP] = 6 x 10-3 mol/m3 doseže povprečna vrednost koncentracije Ca2+ v citoplazmi ([Ca2+]c,pov) svoj minimum. Ker [Ca2+]c,pov močno korelira z razvito silo v GMC, pri enaki vrednosti [cGMP], doseže svoj minimum tudi sila, katere vrednost znaša 25 % maksimalne sile, ki jo je celica sposobna razviti. Pri zelo nizki koncentraciji cGMP ([cGMP]=0,01 x 10-3 mol/m3) pa znaša sila 61 % maksimalne sile. Padec sile v odvisnosti od cGMP je pogojen s spremembo frekvence in amplitude oscilacij Ca2+ v citoplazmi.

Ključne besede

arterije;gladke mišične celice;kalcij;dušikov oksid;kontrakcija;membranska napetost;ionski tokovi;matematični modeli;magistrska dela;

Podatki

Jezik: Slovenski jezik
Leto izida:
Tipologija: 2.09 - Magistrsko delo
Organizacija: UM FNM - Fakulteta za naravoslovje in matematiko
Založnik: [N. Šutar]
UDK: 577:519.8(043.2)
COBISS: 21349384 Povezava se bo odprla v novem oknu
Št. ogledov: 1442
Št. prenosov: 248
Ocena: 0 (0 glasov)
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Ostali podatki

Sekundarni jezik: Angleški jezik
Sekundarni naslov: Modelling of the influence of cyclic guanosine monophosphate (cGMP) on calcium dependent tone of arterial smooth muscle cells
Sekundarni povzetek: In the master thesis we study the influence of increased cyclic guanosine monophosphate (cGMP) levels on the cytosolic calcium (Ca2+) by means of mathematical model accounting for the analysis of force development within vascular smooth muscle cell (SMC). cGMP levels in SMC might increase due to increased shear stress on vessel walls implicating the rise in nitric oxide (NO) production in endothelial cells. NO in turn activates enzyme soluble guanylate cyclase (sGC) producing cGMP in SMC. The main topic of the thesis is the modelling of the impact of cGMP on the Ca2+ signal, and consequently also on the force development in SMC. Four targets of cGMP are considered for modelling: large conductance Ca2+-activated potassium (K+) channels (KCa), Ca2+-dependent chloride (Cl-) channels (ClCa), sodium (Na+) and Ca2+ exchanger (NCX) as well as Na+/K+-ATPase (Na/K). Model also takes into account mathematical descriptions of the voltage-operated Ca2+ channels (VOCC), plasma membrane Ca2+-ATPase (PMCA) and background electric currents of Na+, Cl-, K+ and Ca2+ through plasma membrane. Electric currents of these ions imply the transmembrane potential. The intracellular Ca2+ stores considered are sarcoplasmic reticulum (SR) and Ca2+ buffering proteins. The mechanisms of Ca2+ exchange between the cytosol and the SR taken into account are: Ca2+-ATPase (SERCA), IP3 and Ca2+ dependent channels (ICICR), Ca2+ leak as well as Ca2+ buffering to proteins in the SR and the cytosol. Modelling of the force development in SMC is carried out with the "4-state latch bridge model" upgraded with the Ca2+-dependent regulation of the myosin light chain kinase (MLCK) activity. The development of force in SMC is simulated for concentrations of cGMP ([cGMP]) ranging from 0 to 10 x 10-3 mol/m3. At 6 x 10-3 mol/m3, the mean cytosolic Ca2+ concentration ([Ca2+]c,pov) reaches its minimum and correlates well with the minimum of force being 25 % of the maximal developed force (Fmax). At rather low [cGMP] (i.e. 0,01 x 10-3 mol/m3), the force reaches 61 % of Fmax. The drop of force with respect to increased [cGMP] is due to changes in the frequency and the amplitude of the Ca2+ signal.
Sekundarne ključne besede: arteries;smooth muscles cells;calcium;nitric oxide;contaction;membrane potential;ionic fluxes;mathematical models;master theses;
URN: URN:SI:UM:
Vrsta dela (COBISS): Magistrsko delo/naloga
Komentar na gradivo: Univ. v Mariboru, Fak. za naravoslovje in matematiko, Oddelek za fiziko
Strani: 78 f.
ID: 8751632