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| ZF, 2 ‏كسا‎ NONGATED ION CHANNELS AND THE 3 RESTING MEMBRANE POTENTIAL ad > IN ADDITION TO ATP-POWERED ION PUMPS, WHICH TRANSPORT IONS AGAINSL THEIR CONCENTRATION GRADIENTS **THE PLASMA MEMBRANE CONTAINS CHANNEL PROTEINS THAT ALLOW THE PRINCIPAL CELLULAR IONS (NA+, K+, CA2+, AND CL-) TO MOVE THROUGH THEM AT DIFFERENT RATES DOWN THEIR CONCENTRARRON GRADIENTS. id 5 lysine eam a - ۱ 9 ‏ی‎ en ‏ل فا‎ ne) a 2

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پتانسیل تعادل سدیم Nat* E=-61* aaa 142 mEq/L Co Na E=- 61* ‏سنا‎ ‎E= - 61* log (0.1) E= 61 mv

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Nat Kt 142 mEq/L 4 mEq/L ‏رد‎ ‎Nat ‎14 mEq/L (+61 mV) Ke 140 8 (84 mv) معادله گولدمن - هاجکین - کاتز PNa * Cina + Px * ‏دع إن‎ ۲۳۵۲۰ 0 ۷ go ‏سس‎ ‎PNa * Co Na + PK* Co K + PcL* Ci 0 © ان ت E = -61 Lo

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Outside Kt-Nat "leak" channels -86 mv E = -90 mv So ‏لب‎ YO

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=i “Action Potential ‏بتانسیل عمل‎

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© ‏د و لس ما‎ Getertvay Per Porred Proc Onwerved YD ‏سس‎ Geers ‏ل‎ 0 ‏مج ا‎ fe oor yarisons of the sequences of other K+, Na+, and Ca2* channels established that all such proteins share a n structure and probably evolved from a single type of channel protein (b) Tetrarericchannet Selectivity filter (2) Single subunit

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نأ » Na* ions are smaller than K* ions. How, then' can a channel protein exclude Na* ions, yet allow passage of K*? * The ability of the ion-selectivity filter in K* channels to select K* over Na* is due mainly to backbone carbonyl oxygens on residues located in a Gly an analogous position in the P segment Exoplasmic !: a kK’ in water Nat in water Carbonyl oxygens

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7 مب رس ما ‎Oat Cory tio Oawwdiad Cele War a Deyuive Choe it Pree Euery (BG)‏ » As mentioned earlier, two forces govern the movement of ions across selectively permeable membranes Y the voltage ‏”ا‎ the ion concentration gradient across the membrane > when Na* moves from outside to inside the cell, the free-energy change generated from the Na+ concentration [Na,,] gradient is given by AG, = RT In = 1 Na,,, > Note the free energy is negative, indicating spontaneous movement of Na+ into the cell. تت ‎g ( )‏ كا لت ~

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5 ‎the bree elevirio poteartdl ts vent by‏ مت لس موه روم ۳۰( خ ‎AG,, = FE ‎here @ ip he ‏دسي رول‎ ood @ is he wewbrou eleviic poteuid. If E = -70 mV, then AG-, the free-energy change due to the membrane potential, is - 1.61 kcal ‎AG = AG, + AG, = (-1.45) + (-1.61) = —3.06 kcal/mole ‎

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مت © Wo bicded ‏موم‎ kypert Dooke Bride ood ‏جا0) السو ) صا دا انا‎ epic Wisk Ovureuiratra Brackeuts > Most body cells import glucose from the blood down the concentration gradient of glucose, utilizing GLUT proteins to facilitate this transport. * certain cells, such as those lining the small intestine and the kidney tubules utilize a two-Na+ /one-glucoses symporter; protein that couples import of one glucose molecule to the import of two Na* ions ZNa* ue + glUcOs? gue —= 2 Nain + glucose

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© Glucose Exterior ane Na Glucose Outwarefacing ‏ی‎ Inware-facing Ourwaretfacing Cytosol conformation onformation conformation ۰ conformation 1 | Opercticad cordel Por the tur-(Dertloe_ (Bhoee syxoporter <i Ly J

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| ZF ‏مب‎ ۱ » Consists of 12 membrane-spanning a helices > Two of the helices (numbers 1, and 6) have non helical segments in the middle of the membrane that form part of the leucine-binding site » coupling of substrate and ion transport in these transporters is the consequence of direct or nearly direct physical interactions of the substrates * Indeed, one of the sodium ions is bound to the carboxyl group of the transported ~ leucine, indicating how binding of sodium and leucine are coupled * Each of the two sodium ions is bound to six oxygen atoi wy aN /

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TS / O OatLicked ۵+۵ ‏سوه‎ Exports 0 ۳ ‏مجر‎ Ourdar Disc Orks > In cardiac muscle cells a toree-Na+/ one-Ca2* antiporter. plays the principal role in maintaining a low concentration of Ca2* in the cytosol. 3. Na* our + Ca?* ig == 3 Na* in + Ca” cue > In all muscle cells, a rise in the cytosolic Ca2* concentration in cardiac muscle triggers contraction; by lowering cytosolic Ca'-, operation of the Na+/Ca2+ antiporter reduces the strength of heart muscle contraction. o an) g

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مب رس 7 ‏لكت‎ ‏سیف له صعی ما‎ » inhibition of the Na*/K* ATPase ==> lowers the cytosolic K* concentration and, more relevant here, simultaneously increases cytosolic Na*. Y The resulting reduced Na* electrochemical gradient across the membrane causes the Na+-linked Ca2* antiporter to function less efficiently ¥ cytosolic Ca2* concentration increases, causing the muscle to contract more strongly. 9 Y drugs such as ouabain and digoxin that inhibit the Na-/K- ATPase are widely used in the treatment of congestive heart failure ‎aN /‏ ش) تا ۲

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مب رس 7 ‏لت‎ ‏يك‎ 0 Requate Opirscle pL » The anaerobic metabolism of glucose yields lactic acid, and aerobic metabolism yields CO2, which adds water to form carbonic acid (H2CO3). These weak acids dissociate yielding H- ions (protons) if these excess protons were not removed from cells, the cytosolic pH would drop precipitously, endangering cellular functions Two types of cotransport proteins help remove some of the "excess" protons generated during metabolism in animal cells * One is a Na* Hco, / Cl antiporter = * Hco; / Cl antiporter Ly

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۵2 0۵6 ‏یم۲۱ ۱۱۵۲ و وا‎ / Cl antiporter » imports one Na+ ion together with one HCO3-, in exchange for export of one Cl ion. » The cytosolic enzyme carbonic anhydrase catalyzes dissociation of the imported HCO3- ions into CO2 and an OH- (hydroxyl)ion: HCO;- == CO, + OH ¥ The OH- ions combine with intracellular protons, forming water, and the CO2 diffuses out of the cell. Thus the overall action of this transporter is to consume cytosolic H+ ions, thereby raising the cytosolic pH. © Also importanr in raising cytosolic pH is a Na* /H* antiporter, which couples entry of one Na* ion into the cell down its concenrration gradient to the export of one H+ ron ۸ 4- لها نما د

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مب رس ۵۲ ۱ | ۲۱6۵ لا » beyond the normal range of 7 .2-7.5. To cope with the excess OH- ions associated with elevated pH, many animal cells utilize an anion antiporter that catalyzes Y the one-for-one exchange of HCO3- and Cl across the plasma membrane ¥ Athigh pH, this C/ /HCO3- antiporter exports HCO3- (which can be viewed as a "complex" of OH and CO2) in exchange for import of Cl-, thus lowering the cytosolic pH.

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