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Ebook Cellular physiology and neurophysiology (2th edition): Part 2

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Nội dung chi tiết: Ebook Cellular physiology and neurophysiology (2th edition): Part 2

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2al gradients.2Understand how Gà’* is sequestered in the sarcoplasmic and endoplasmic reticulum and transported across the plasma membrane by ATP depen

dent active trans port systems.3Understand how intracellular Cù’1 is controlled and Ca’1 signaling IS regulated by the cooperative action or many tran Ebook Cellular physiology and neurophysiology (2th edition): Part 2

sport systems.4. Understand the roles of AlP-dependent transport systems in the transport of such ions as protons and copper, as well as a variety of

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

other solutes.s. Understand how different transport systems in the apical and basolaleral membranes OÍ epithelia, which separate two different extrace

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2CALENERGY FROM ATP INTO ELECTROCHEMICAL POTENTIAL ENERGY STORED IN SOLUTE GRADIENTSIn Chapter 10, we learned how energy stored in the Na' electrochemi

cal gradient can be used to gener ate concentration (or electrochemical) gradients for other (coupled) solutes. This is called secondary active transp Ebook Cellular physiology and neurophysiology (2th edition): Part 2

ort because a preexisting electrochemical energy gradient is dissipated in one part of the transport process (e.g., the downhill movement of Na+) to g

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

enerate the chemical or electrochemical gradients of other solutes (e.g., glucose or Ca2T There is no net expenditure of metabolic energy by these tra

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2n the first place? This brings US to the role of ATP in powering primary active transport. During active ion transport, adenos ine triphosphatases (AT

Pases) interconvert chemical (phosphate bond) energy and electrochemical poten tial (ion gradient) energy. These straightforward chem ical reactions c Ebook Cellular physiology and neurophysiology (2th edition): Part 2

an, depending on the concentrations of substrates and products, operate in cither the forward or the reverse direction; that is, they can either use (

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

hydrolyze) or synthesize ATP.Three Broad Classes of ATPases Are Involved in Active Ion Transportrhe three classes of ion transport ATPases are the F-,

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2rochemical gradient across the inner mitochondrial membrane; the proton gradient is generated by oxidative metabolism. Vacuolar (V-type) ll+-ATPases l

ower intraorganel-lar pH by concentrating protons in a variety of vesicular organelles, including lysosomes and secretory and storage vesicles. Neithe Ebook Cellular physiology and neurophysiology (2th edition): Part 2

r the F-type nor the V-type ATPases form stable phosphorylated intermediates. P-type ATPases, which do form stable phosphorylated intermediates that c

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

an be isolated chemically, transport numerous ions and other solutes into and out of cells and organelles. Examples of P-type ATPases are the PM Na pu

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2ump (111 ,K -ATPasc). These P-Lypc A'l Pases are the focus of much ol this chapter.THE PLASMA MEMBRANE Na+ PUMP (Na+,K*-ATPase) MAINTAINS THE LOW Na+

AND HIGH K+ CONCENTRATIONS IN THE CYTOSOLNearly All Animal Cells Normally Maintain a High Intracellular K1 Concentration and a Low Intracellular Na+ C Ebook Cellular physiology and neurophysiology (2th edition): Part 2

oncentrationIn most cells in mammals, including humans, [K' Ji::: 120 130 mM, and [Na1 Ji ■■■■■ 5 15 mM. The extracellular fluid, however, has a high

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

[Na L <-—145 mM) and a low K' concentration [K']o (~4 3 mM). Moreover, cells are not impermeable to Na1 and K: Na ‘ and K ‘ chan nels and Na gradient

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2adients. Therefore, all cells expend energy in the form of ATP to generate and maintain their normal Na* and K‘ electrochemical gradients. The transpo

rter that accomplishes this work is the sodium pump or Na+,K+-ATPasc. In the nervous system and the kidneys, the Na+ pump accounts for a very large fr Ebook Cellular physiology and neurophysiology (2th edition): Part 2

action (75% to 85%) of total ATP hydrolysis. The transport of Na+ and K+ by the Na+ pump compensates for the leak of these ions into and out of the ce

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

ll, respectively. This is known as the pump-leakmodel of Na+ and K* homeostasis. The Na+ pump not only maintains constant [Na^Land [K+]j,but also infl

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2rting Na+ Out of the Cell and K+ Into the CellThe Na' pump is an integral PM protein whose major (a, or “catalytic”) subunit has 10 membrane-spanning

helices (Figure 11-1) and contains the ATP and ion binding sites. The a-subunit is closely associated with a smaller, highly glycosylated, |3 subunit Ebook Cellular physiology and neurophysiology (2th edition): Part 2

that has a single membrane-spanning domain. Complexes of <»- and [i-subunits, in a 1:1 ratio, are required for Na 1 pump activity, but how the p-subun

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

il functions is unknown, rhe Na1 pump is frequently called the Na*,K*-.'\TPase because the protein is an enzymethe a- (catalytic) subunit of the Na pu

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 24 and 5 contains the ATP binding domain (shown) and the aspartate phosphorylation site. The ion binding sites arc located in transmembrane helices 4,

5, 6, and 8. Residues that bind ouabain are located on the external surfaces of helices 1, 2, 5, 6, and 7, thus, bound ouabain may block access to the Ebook Cellular physiology and neurophysiology (2th edition): Part 2

cation binding sites. (Modified from Lingrcl JB, Crọylc ML, Woo AL, et al: Acta Physiol Scand Suppl 643:69, 1998.)Av live IK«H5rUKIIJJ(specifically,

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

an ATPase) that requires both Na* and K* for its catalytic activity (ATP hydrolysis).*The Na+ pump hydrolyzes 1 ATP molecule to ADP and inorganic phos

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2ATP complex) at the hydrolytic site on the a-subunit (Figure 11-1). When 3 Na’ ions bind to the pump on the cytoplasmic side, the ATP is cleaved and i

ts terminal, high-energy phosphate is transferred to the a-subunit. This phosphorylation enables the protein to undergo a conformational change so tha Ebook Cellular physiology and neurophysiology (2th edition): Part 2

t the bound Na' becomes transiently inaccessible (“occluded”) to both the intracellular and extracellular fluids. The Na' binding site then opens to t

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

he extracellular fluid. This conformational change also markedly reduces the Na ' affinity, while greatly increasing K ' affinity. Thus, the 3 Na+ ion

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2—phosphate bond is cleaved, Pi is released into the cytoplasm, and the K* binding sites close to the external surface (Ĩ.C., the 2 K* ions arc transie

ntly occluded) and then open to the internal surface. The 2 K + ions arc released into the cytoplasm because the affinity for K+ decreases markedly du Ebook Cellular physiology and neurophysiology (2th edition): Part 2

ring this conformational change. This sequence of steps in the Na+ pump cycle is ilhis trated in Figure 11 2A.The net reaction for the Na' pump can be

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

written as Equation [1]:3 Na+.y, t 2 K+rcr + 1 ATP.,,3 Na^ 4 2 K-% + 1 ADPq, + 1 Pi^This net reaction can be diagrammed as shown in Figure 11 2B. Not

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2he substrate concentrations are greatly reduced.As a result of the 3 Na+:2 K+ coupling ratio, inhibition of the Na+ pump will lead to a net gain of so

lute•The Na’.K’-ATPav was identified in 1957 by lens skou. He was awarded the Nobel Prize tor this work in 1997.(as Na+ salts, to maintain electroneut Ebook Cellular physiology and neurophysiology (2th edition): Part 2

rality) and a rise in osmotic pressure. The cells will therefore gain water and swell (see discussion of the Donnan effect in Chapter 4). Thus the Na+

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

pump participates directly in cell volume maintenance.The Na+ Pump Is “Electrogenic”The reaction sequence (Equation (11) reveals that during each Na'

OBJECTIVES1Understand how the Na ' pump uses energy from Al p to keep [Na ] low and [K' ]| high by transporting Na and K’ against their electrochemica

Ebook Cellular physiology and neurophysiology (2th edition): Part 2s a small voltage (cytoplasm negative). The Na pump is therefore said to be electrogenic. Indeed, this voltage adds to the Vni, so that the actual res

ting VOI is slightly more negative than the Vm calculated from the Goldman-1 lodgkin-Katz (Cl IK) equation (see Chapter 4). The maximum voltage that c Ebook Cellular physiology and neurophysiology (2th edition): Part 2

an Ik* generated by the Na 1 pump with a coupling ratio ol 3 Na 2 K+, under steady-stale conditions, is approximately 10 mV. In practice, however, the

Ebook Cellular physiology and neurophysiology (2th edition): Part 2

contribution ol the eleclrogenic Na+ pump to the resting Vm (i.e., in the steady slate) in most cells is only a few millivolts (I to 4 mV) and is usu

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