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Phy 1

Aufbau und Funktion der Zellmembran

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Objectives Phy-1

• Beschreibe die Membran-Eigenschaften in Relation zu den Komponenten

• Erläutere die Bedeutung von Membran-Innenphospholipidenund Membran-Aussenphospholipiden

• Erkläre die Bedeutung von ungesättigten FS und von Cholesterin in der Membran

• Benenne die Substanze, welche direkt durch die Phospholipidmembran diffundieren

• Erkläre die Bedeutung von Membranen für die intrazelluläre Kompartmentierung

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Inhalte

• Impermeabilität gegenüber polaren Substanzen• Permeabel gegen N2, CO2, O2, CO, NO• Permeabilität gegenüber Wasser• PC/PS Eigenschaften, Cholesterin, Sphingomyeline,

Glykolipide• Kompartmentierung

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Die Zytoplasma-Membran•Kommunikation mit der Außenwelt (über Rezeptoren, Ionenkanäle...); Kommunikation mit Nachbarzellen (z.B. über „gap-junctions“); Konzentration verschiedener Protein- und Signalkomplexe, Verankerung mit dem Zytoskelett, Aufrechterhaltung der Polarität spezieller Zellen (z.B. Leberparenchymzellen) über sogenannte „tight junctions“ etc.

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Figure 10-1. Three views of a cell membrane. (A) An electron micrograph of a plasma membrane (of a human red blood cell) seen in cross-section. (B and C) Schematic drawings showing two-dimensional and three-dimensional views of a cell membrane. (A, courtesy of Daniel S. Friend.)

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Membraneigenschaften

• Durchlässigkeit für Gase (CO2, O2, NO, CO)• Durchlässigkeit für Wasser (minimal und wenn Sphingomyeline

in Membran völlig negativ, Wasserporen• Alle geladenen bzw. polaren Partikel nur durch

Transportsysteme (Ionen, etc)• Lipide: eigentlich nicht durch Membran sondern über ABC

Transporter oder andere Mechanismen

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Figure 11-1. The relative permeability of a synthetic lipid bilayer to different classes of molecules. The smaller the molecule and, more important, the fewer hydrogen bonds it makes with water, the more rapidly the molecule diffuses across the bilayer.

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Figure 11-12. Response of a human red blood cell to changes in osmolarity(also called tonicity) of the extracellular fluid. Because the plasma membrane is freely permeable to water, water will move into or out of cells down its concentration gradient, a process called osmosis. If cells are placed in a hypotonic solution (i.e., a solution having a low solute concentration and therefore a high water concentration), there will be a net movement of water into the cells, causing them to swell and burst (lyse). Conversely, if cells are placed in a hypertonic solution, they will shrink.

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Membranphospholipide

• Verteilung der PL• PC vs PS und Funktion (Kalziumbindung, Gerinnung

aussen und PKC innen)• GPI, rafts, Cavoleae• Cholesterin

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The parts of a phospholipid molecule. Phosphatidylcholine, represented schematically (A), in formula (B), as a space-filling model (C), and as a symbol (D). The kink due to the cis-double bond is exaggerated in these drawings for emphasis.

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Figure 10-10. Four major phospholipids in mammalian plasma membranes. All of the lipid molecules shown are derived from glycerol except for sphingomyelin, which is derived from serine.

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Figure 5-27. Structures of two types of phospholipids and a glycolipid. The hydrophobic portions are shown in yellow; the hydrophilic, in green. (a) Phosphatidylcholine (b) Sphingomyelins are a group of phospholipids that lack a glycerol backbone; Linkage of sphingosine (outlined by black dots) to a fatty acid via an amide bond forms a ceramide. (c) Glucosylcerebroside, one of the simplest glycolipids, consists of the ceramide formed from sphingosine and oleic acid linked to a single glucose residue. This glycolipid is abundant in the myelin sheath.

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Almost all the sphingomyelin and phosphatidylcholine, both of which have a positively charged head group are found in the exoplasmic leaflet.

In contrast, lipids with neutral or negative polar head groups (e.g., phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol) are preferentially located in the cytosolic leaflet.

The relative abundance of a particular phospholipid in the two leaflets of a plasma membrane can be determined based on its susceptibility to hydrolysis by phospholipases, enzymes that cleave the phosphoester bonds that connect the phospholipid head groups

Phospholipid assymetry

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Figure 10-11. The asymmetrical distribution of phospholipids and glycolipids in the lipid bilayer of human red blood cells.

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Table 10-1. Approximate Lipid Compositions of Different Cell Membranes

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Eigenschaften der PL-headgroups

PS: Ca++ binding, Gerinnung (=Faktor III), PKC

PC: PLA2 –free fatty acids

PE: wird zu PC umgewandelt; PLA2

PI: GPI-anchor, Signaling (IP3), PLC

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Figure 10-6. Phospholipid mobility. The types of movement possible for phospholipid molecules in a lipid bilayer.

Figure 10-7. Influence of cis-double bonds in hydrocarbon chains. The double bonds make it more difficult to pack the chains together and therefore make the lipid bilayermore difficult to freeze.

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Eigenschaften von Fettsäuren:

Menge der ungesättigten Fettsäuren abhängig von der Nahrungsaufnahme

Aus mehrfach ungesättigten FS (PUFAs) entstehen wichtige Lipidmediatoren

Je mehr ungesättigte FS in der Membran, desto durchlässiger ist jene für Wasser (viele Sphingomyeline-undurchlässig)

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Figure 3-37. Specificity of cleavage of phospholipids by phospholipases A1, A2, C, and D.Susceptible bonds are shown in red. R denotes the polar group attached to the phosphate, such as choline in phosphatidylcholine or inositol in phosphatidylinositol

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Figure 10-8. The structure of cholesterol. Cholesterol is represented by a formula in (A), by a schematic drawing in (B), and as a space-filling model in (C).

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Membran Mikrodomänen („Rafts“):

Reich an Sphingomyelinen und Cholesterin und Signalmolekülen

Caveoli

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Figure 10-41. Simplified diagram of the cell coat (glycocalyx). The cell coat is made up of the oligosaccharide side chains of glycolipids and integral membrane glycoproteins and the polysaccharide chains on integral membrane proteoglycans. In addition, adsorbed glycoproteinsand adsorbed proteoglycans (not shown) contribute to the glycocalyx in many cells. Note that all of the carbohydrate is on the noncytoplasmic surface of the membrane.

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Eines der wesentlichsten Charakteristika aller bis jetzt gefundenen Lebensformen ist ihre Abgrenzung von der Umwelt; also die Kompartimentierung ihrer eigenen Organisationsform.

Erst diese Abgrenzung ermöglicht das Auftreten von elektrochemischen Gradienten, und damit die Existenz energetischer Potentialdifferenzen.

Die Tendenz zum Ausgleich dieser Differenzen in Form eines Fließgleichgewichts macht die Aufrechterhaltung eines höheren Ordnungszustandes innerhalb dieses Kompartiments möglich, und somit die temporär und räumlich begrenzte Reduktion des Entropiegrades (Negentropie).

Kompartimentierung als Grundlage für Leben

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Prinzipielle Eigenschaften von Kompartimenten

•Kompartimente sind Reaktionsräume•Diese Reaktionsräume sind normalerweise durch einen Lipid-Bilayer vom Außenraum abgegrenzt.•Hydophobe Substanzen und kleine ungeladene Moleküle (wie z.B. O2) können meist durch die Lipidbarriere diffundieren. Hydrophile oder geladene Moleküle, sowie die meisten Makromoleküle können nicht passiv durch die Membran diffundieren.•In die Membran eingebette Proteine (integrale Membranproteine) oder an die Membran assoziierte Proteine (periphere Membranproteine) können wesentliche Steuerungsfunktionen ausüben (wie etwa aktive Transportprozesse durch die Membran, Aufbau elektrochemischer Gradienten, Interaktionen mit anderen Makromolekülen etc.).

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Plasmatische und nicht-plasmatische Phasen von Eukaryonten

•Die äußere Zellmembran trennt die cytoplasmatische Phase der Zelle von der extracytoplasmatischen Phase der Umgebung ab. Äquivalent dazu können die Innenräume intrazellulärer Kompartimente, die von einem einfachen Lipid-Bilayer umgeben sind, als nicht-plasmatische Phasen angesehen werden (ER, Golgi, sekretorische Vesikel, Endosomen, Lysosomen etc.). Ihr Inneres entspricht somit in gewisser Weise dem Extrazellulärraum. •Plasmatische Phasen der Zelle sind das Cytosol, sowie das Innere von Kompartimenten, die von einem doppelten Lipid-Bilayerumgeben sind (Zellkern, Mitochondrien, Chloroplasten). Die Zwischenräume zwischen den beiden Membranen dieser Kompartimente zählen zu den nicht-plasmatischen Bereichen.

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Block 3Phy 2

Aktiver Transport

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Objectives Phy-2

• Zähle unterschiedliche Transportmechanismen für polare Substanzen durch die Zellmembran auf

• Benenne unterschiedliche aktive Transportmechanismen in der Zelle• Beschreibe die Funktionsweise der Na-K-Pumpe• Beschreibe charakteristische Eigenschaften der drei P-typ Pumpen• Benenne V-typ und F-typ Pumpen• Zähle unterschiedliche ABC Transporter und deren Substrate auf

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Table 11-1. Comparison of Ion Concentrations Inside and Outside a Typical Mammalian Cell

Component

Intracellular Concentration (mM)

Extracellular Concentration (mM)

CationsNa+ 5-15 145K+ 140 5Mg2+ 0.5 1-2Ca2+ 10-4 1-2H+ 7 x10-5 (10-7.2M

or pH 7.2)4x10-5 (10-7.4 M

or pH 7.4)Anions*Cl- 5-15 110

*. The cell must contain equal quantities of + and - charges (that is, be electrically neutral). Thus, in addition to Cl-, the cell contains many other anions not listed in this table; in fact, most cellular constituents are negatively charged (HCO3

-, PO43-, proteins, nucleic acids, metabolites carrying

phosphate and carboxyl groups, etc.). The concentrations of Ca2+ and Mg2 + given are for the free ions. There is a total of about 20 mM Mg2+ and 1-2 mM Ca2+ in cells, but this is mostly bound to proteins and other substances and, in the case of Ca2+, stored within various organelles.

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Figure 11-3. A schematic view of the two classes of membrane transport proteins. A carrier protein is thought to alternate between two conformations, so that the solute binding site is sequentially accessible on one side of the bilayer and then on the other. In contrast, a channel protein is thought to form a water-filled pore across the bilayer through which specific ions can diffuse.

Figure 11-4. Comparison of passive transport down an electrochemical gradient with active transport against an electrochemical gradient. Whereas simple diffusion and passive transport by membrane transport proteins (facilitated diffusion) occur spontaneously, active transport requires an input of metabolic energy. Only carrier proteins can carry out active transport, but both carrier proteins and channel proteins can mediate facilitated diffusion.

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Figure 15-3. Schematic diagrams illustrating action of membrane transport proteins. Gradients are indicated by triangles with the tip pointing toward lower concentration, electrical potential, or both. (a) The three major types of transport proteins. Pumps utilize the energy released by ATP hydrolysis to power movement of specific ions (red circles) or small molecules against their electrochemical gradient. Channels catalyze movement of specific ions (or water) down their electrochemical gradient. Transporters, which fall into three groups, facilitate movement of specific small molecules or ions (black circles). (b) The three groups of transporters. Uniporters, also shown in part (a), transport a single type of molecule down its concentration gradient. Cotransport proteins (symporters and antiporters) catalyze the movement of one molecule against its concentration gradient (black circles), driven by movement of one or more ions down an electrochemical gradient (red circles). The two types of cotransporters differ in the relative direction of movement of the transported molecule and cotransported ion.

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Figure 15-10. The four classes of ATP-powered transport proteins.P-class pumps are composed of two different polypeptides, a and ß, and become phosphorylated as part of the transport cycle. The sequence around the phosphorylated residue, located in the larger a subunits, is homologous among different pumps.

F-class and V-class pumps do not form phosphoprotein intermediates. Their structures are similar and contain similar proteins, but none of their subunits are related to those of P-class pumps.

All members of the large ABC superfamily of proteins contain four core domains: two transmembrane (T) domains and two cytosolic ATP-binding (A) domains that couple ATP hydrolysis to solute movement. These core domains are present as separate subunits in some ABC proteins (depicted here), but are fused into a single polypeptide in other ABC proteins.

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Figure 11-10. The Na+-K+ ATPase. This carrier protein actively pumps Na+ out of and K+ into a cell against their electrochemical gradients. For every molecule of ATP hydrolyzed inside the cell, three Na+ are pumped out and two K+ are pumped in. The specific pump inhibitor ouabain and K+ compete for the same site on the external side of the ATPase.

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Figure 15-13. Models for the structure and function of the Na+/K+ ATPase in the plasma membrane. (a) This P-class pump comprises two copies each of a small glycosylated ß subunit and a large a subunit, which performs ion transport. Hydrolysis of one molecule of ATP to ADP and Pi is coupled to export of three Na+ ions (blue circles) and import of two K+ ions (dark red triangles) against their concentration gradients (large triangles). It is not known whether only one a subunit, or both, in a single ATPase molecule transports ions. (b) Ion pumping by the Na+/K+ ATPaseinvolves a high-energy acyl phosphate intermediate (E1~P) and conformational changes, similar to transport by the muscle Ca2+ ATPase. In this case, hydrolysis of the E2 – P intermediate powers transport of a second ion (K+) inward. Na+ ions are indicated by blue circles; K+ ions, by red triangles. See text for details. [Adapted from P. Läuger, 1991, Electrogenic Ion Pumps, Sinauer Associates, p. 178.]

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Figure 15-11. Model of the mechanism of action of muscle Ca2+ ATPase, which is located in the sarcoplasmic reticulum (SR) membrane. Only one of the two a subunits of this P-class pump is depicted. E1 and E2 are alternate conformational forms of the protein in which the Ca2+-binding sites are on the cytosolic and exoplasmic faces, respectively. An ordered sequence of steps, as diagrammed here, is essential for coupling ATP hydrolysis and the transport of Ca2+ ions (red circles) across the membrane. ~P indicates a high-energy acyl phosphate bond; — P indicates a low-energy phosphoester bond. See the text for more details. [Adapted from W. P. Jencks, 1980, Adv. Enzymol. 51:75; W. P. Jencks, 1989, J. Biol. Chem.264:18855; and P. Zhang et al., 1998, Nature 392:835.]

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Figure 11-16. A schematic drawing of a typical ABC transporter. (A) Topology diagram. (B) Hypothetical arrangement of the polypeptide chain in the membrane. The transporter consists of four domains: two highly hydrophobic domains, each with six putative

membrane-spanning segments that somehow form the translocation pathway, and two ATP-binding catalytic domains (or cassettes). In some cases the two halves of the transporter are formed by a single polypeptide (as shown ), whereas in other cases they are formed by two separate polypeptides

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Figure 15-16. Schematic structural model for mammalian MDR1 protein.

In this member of the ABC superfamily, the two transmembrane domains and two cytosolic ATP-binding domains are part of a single polypeptide.Each transmembrane domain contains six a helices. The two halves of this 1280-aa protein have similar amino acid sequences. A variety of lipid-soluble molecules that diffuse across the plasma membrane into the cell are transported outward by MDR1

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Figure 15-17. Possible mechanisms of action of the MDR1 protein.(a) The flippase model proposes that a lipid-soluble molecule first dissolves in the cytosolic-facing

leaflet of the plasma membrane ( 1 ) and then diffuses in the membrane until binding to a site on the MDR1 protein that is within the bilayer ( 2 ). Powered by ATP hydrolysis, the substrate molecule flips into the exoplasmic leaflet ( 3 ), from which it can move directly into the aqueous phase on the outside of the cell ( 4 ).

(b) According to the pump model, MDR1 has a single multisubstrate binding site and transports molecules by a mechanism similar to that of other ATP-powered pumps.

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Family Representative MembersSugar transporters passive glucose transporters in mammalian cells

some H+-driven sugar transporters in bacteria

Cation-transporting ATPases Na+-K+ ATPases; Ca2+ ATPases

ABC transporters multidrug resistance (MDR) ATPase in mammalian cells; periplasmic substrate-binding-protein-dependent ATPases in bacteria; chloroquine-resistance ATPase in P. falciparum; mating pheromone exporter in yeast; peptide pump in vertebrate ER membrane; cystic fibrosis transmembrane regulator (CFTR) protein

Anion (Cl--HCO3-) antiporters band 3 in red blood cells; anion exchangers in

other cells

Cation antiporters Na+-H+exchanger

Cation/anion antiporters Na-dependent Cl--HCO3- exchanger

Na+-driven symporters Na+-glucose symporter in intestinal cells; Na+-proline symporter in bacteria; Na+-HCO3

-

symporter in glialcells

Table 11-2. Some Carrier Protein Families

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Objectives Phy-3

• Benenne passive Ionentransporter durch die Zellmembran und treibende Kräfte

• Beschreibe wichtige Typen von Ionenkanälen• Beschreibe die Funktion der wichtigsten Antiporte und Symporte• Beschreibe Transportmechanismen für Glucose und

Aminosäuren durch die Membran• Beschreibe das Vorkommen von Wasserkanälen und deren

Bedeutung

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Transportmechanismen

• Nicht-ATPasen– Austauscher (Antiporte) Cl/Bicarbonat, Na/H, Na/Ca,– Cotransporte (Symporte) Na-Phosphat, Na-Bicarbonat, Na-K-Cl,

Nichtionale (SGlut, AS)– Kanäle

• Na (gated vs non gated)• K (gated vs non gated)• Ca (gated vs non gated)• Cl (gated vs non gated)• Wasser

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Kanäle:Gated channels,Ligand-induced,Stretch-activated (Ca)ATP-inhibited (K)

Antiport:H-Na TauscherCl-HCO3 Tauscher (Erythrozyten, CO2 Transport,

HCO3 Rücktransport i.d. Niere,Volumensregulation)

Na-Ca Tauscher (Herz)

Symport:Na-K-Cl (Niere, Speichel)Na-PO4 (Niere, Phosphatrücktransport)Na-GlukoseNa-Aminosäuren

Andere für Glukose:GLUT 1,2

Wasser:Aquaporine

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Figure 11-8. Three types of carrier-mediated transport. The schematic diagram shows carrier proteins functioning as uniports, symports, and antiports.

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Figure 15-4. Liposomes containing a single type of transport protein can be used to investigate properties of the transport process. Here, all the integral proteins of the erythrocyte membrane are solubilized by a nonionic detergent, such as octylglucoside. The glucose transport protein, a uniporter, can be purified by chromatography on a column containing a specific monoclonal antibody and then incorporated into liposomes made of pure phospholipids.

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Figure 15-5. Comparison of the observed uptake rate of glucose by erythrocytes (red curve) with the calculated rate if glucose were to enter solely by passive diffusion through the phospholipid bilayer (blue curve). The rate of glucose uptake (measured as micromoles per milliliter of cells per hour) in the first few seconds is plotted against the glucose concentration in the extracellula r medium. In this experiment the initial concentration of glucose in the erythrocyte is zero, so that the concentration gradient of glucose across the membrane is the same as the external concentration. The glucose transporter in the erythrocyte membrane clearly increases the rate of glucose transport, compared with that associated with passive diffusion, at all glucose concentrations. Like enzymes, the transporter-catalyzed uptake of glucose exhibits a maximum transport rate Vmax and is said to be saturable . The Km is the concentration at which the rate of glucose uptake is half-maximal.

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Figure 15-7. Model of the mechanism of uniport transport by GLUT1, which is believed to shuttle between two conformational states. In one conformation ( 1 , 2 , and 5 ), the glucose-binding site faces outward; in the other ( 3 , 4 ), the binding site faces inward. Binding of glucose to the outward-facing binding site ( 1 ? 2 ) triggers a conformational change in the transporter ( 2 ? 3 ), moving the bound glucose through the protein such that it is now bound to the inward-facing binding site. Glucose can then be released to the inside of the cell ( 3 ? 4 ). Finally, the transporter undergoes the reverse conformational change ( 4 ? 5 ), inactivating the inward-facing glucose binding site and regenerating the outward-facing one. If the concentration of glucose is higher inside the cell than outside, the cycle will work in reverse ( 4 ? 1 ), catalyzing net movement of glucose from inside to out.

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Figure 15-9. Transmembrane forces acting on Na+ ions. As with all ions, the movement of Na+ ions across the plasma membrane is governed by the sum of two separate forces — the membrane electric potential and the ion concentration gradient. In the case of Na+ ions, these forces usually act in the same direction.

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Figure 11-18. Gated ion channels. Schematic drawing of the different ways in which ion channels are gated.

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Figure 11-21. The voltage-gated Na+ channel can adopt at least three conformations (states). When the membrane is at rest (highly polarized), the closed conformation has the lowest free energy and is therefore most stable; when the membrane is depolarized, the energy of the open conformation is lower and so the channel has a high probability of opening.

But the free energy of the inactivated conformation is lower still, and so, after a randomly variable period spent in the open state, the channel becomes inactivated. Thus the open conformation corresponds to a metastable state that can exist only transiently.

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Table 11-3. Some Ion Channel Families

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Figure 15-18. Structural model for the two-Na+/one-glucose symporter.This 662-aa protein forms 14 transmembrane a helices with the N-and C-termini facing the cytosol. The five C-terminal helices form the sugar-permeation pathway; the rest of the protein may be required to couple Na+ binding and glucose transport. The exoplasmic surface of the protein has binding sites for two Na+ ions and one glucose.

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Figure 15-19. Proposed model for operation of the two-Na+/one-glucose symporter.The simultaneous binding of Na+ and glucose to sites on the exoplasmic surface induces a conformational change, generating a transmembrane pore or tunnel that allows both bound Na+ and glucose to move through the protein to binding sites on thecytosolic domain and then to pass into the cytosol. After this passage, the protein reverts to its original conformation.

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Figure 15-20. Schematic drawings showing anion transport across the erythrocyte membrane in systemic and pulmonary capillaries. AE1 protein (purple) — an anion antiporter — catalyzes the reversible exchange of Cl- and HCO3

- ions across the membrane and works in conjunction with carbonic anhydrase. In systemic capillaries, the overall reaction causes HCO3

- to be released from the cell, which is essential for CO2 transport from the tissues to the lungs. In the lungs, the overall reaction is reversed.

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Modell der Wirkungsweise spannungsgesteuerter Na+-Kanäle

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Figure 15-33. The structure of aquaporin, a water-channel protein in the erythrocyte plasma membrane. This tetrameric protein has four identical subunits.

(a) Schematic model of an aquaporin subunit showing the three pairs of homologous transmembrane a helices, A and A', B and B', and C and C'. As indicated by the arrows showing the N-terminal ? C-terminal directionality of the helices, the homologous segments are oriented in the opposite direction.

(b) Head-on view of tetrameric aquaporin showing the packing of the transmembrane a helices in the plane of the membrane, as determined by x-ray crystallography. The helices (represented as circles) in each of the four subunits are shown in different colors.

The opposite orientation of the two helices in a pair within the membrane would account for the ability of the channel to transport water equally in both directions across the membrane.

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Objectives Phy-4

• Beschreibe die Wasserresoprtion durch Epithelien• Bringe Bespiele für die wichtigsten sezernierenden Typen von

Epithelien• Bringe Beispiele für die wichtigsten Typen von resorbierenden

Epithelien• Erkläre die Entstehung von Sekreten im Organismus• Erkläre die Bedeutung von Ionentransporten für andere

Zelleigenschaften•

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Folgen für Epithelien,Sekretion, Resorption

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Figure 11-13. The transcellular transport of glucose across an intestinal epithelial cell depends on the asymmetrical distribution of transport proteins in the cell's plasma membrane . The process shown results in the transport of glucose from the gut lumen to the extracellular fluid (from where it passes into the blood). Glucose is pumped into the cell through the apical domain of the membrane by a Na+-powered glucose symport, and glucose passes out of the cell (down its concentration gradient) by facilitated diffusion mediated by a different glucose carrier protein in the basal and lateral membrane domains. The Na+ gradient driving the glucose symport is maintained by the Na+-K+ ATPase in the basal and lateral plasma membrane domains, which keeps the internal concentration of Na+ low.Adjacent cells are connected by impermeable junctions (called tight junctions). The junctions have a dual function in the transport process illustrated: they prevent solutes from crossing the epithelium between cells, allowing a concentration gradient of glucose to be maintained across the cell sheet, and they also serve as diffusion barriers within the plasma membrane, which help confine the various carrier proteins to their respective membrane domains (see Figure 10-37).

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Figure 15-23. Schematic diagram of epithelial cells lining the small intestine and the principal types of cell junctions that connect them. As in all epithelia, the basal surface of the cells rests on the basal lamina, a fibrous network of collagen and proteoglycans that supports the epithelial cell layer. The apical surface faces the intestinal lumen. Tight junctions, lying just under the microvilli, prevent diffusion of substances between the intestinal lumen and the blood via the extracellular space between cells. Gap junctions allow movement of small molecules and ions between the cytosol of adjacent cells. The remaining three types of junctions, adherens junctions, spot desmosomes, and hemidesmosomes are critical to cell-cell and cell-matrix adhesion.

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Figure 15-25. Transport of glucose from the intestinal lumen into the blood. Activity of the Na+/K+

ATPase (green) in the basolateral surface membrane generates Na+ and K+ concentration gradients, and the K+ gradient generates an inside-negative membrane potential. Both the Na+ concentration gradient and the membrane potential are used to drive the uptake of glucose from the intestinal lumen by the two-Na+/one-glucose symporter (blue) located in the apical surface membrane. Glucose leaves the cell via facilitated diffusion catalyzed by GLUT2 (orange), a glucose uniporter located in the basolateral membrane.

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Figure 15-26. Acidification of the stomach lumen by parietal cells in the gastric lining. The apical membrane of parietal cells contains a H+/K+ ATPase (a P-class pump) as well as Cl- and K+ channel proteins. Note the cyclic K+ transport across the apical membrane: K+ ions are pumped inward by the H+/K+ ATPaseand exit via a K+ channel. The basolateral membrane contains an anion antiporter that exchanges HCO3

- and Cl- ions. The combined operation of these four different transport proteins acidifies the stomach lumen while maintaining the neutral pH and electroneutralityof the cytosol. See the text for more details.