Chapter 2 Psychological Methods. 2 Chapter 2 Chapter 2: Section 1 Conducting Research.
Chapter 2
description
Transcript of Chapter 2
![Page 1: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/1.jpg)
Chapter 2
Transport of ions and small molecules across membranes
ByStephan E. Lehnart & Andrew R. Marks
![Page 2: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/2.jpg)
2.1 Introduction
• Cell membranes define compartments of different compositions.
• The lipid bilayer of biological membranes has a very low permeability for most biological molecules and ions.
![Page 3: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/3.jpg)
• Most solutes cross cell membranes through transport proteins.
• The transport of ions and other solutes across cellular membranes controls:– electrical functions – metabolic functions
2.1 Introduction
![Page 4: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/4.jpg)
2.2 Channels and carriers are the main types of membrane transport proteins
• There are two principal types of membrane transport proteins: – Channels– Carriers
![Page 5: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/5.jpg)
• Ion channels catalyze the rapid and selective transport of ions down their electrochemical gradients.
• Transporters and pumps are carrier proteins.– They use energy to transport solutes against their
electrochemical gradients.
• In a given cell, several different membrane transport proteins work as an integrated system.
2.2 Channels and carriers are the main types of membrane transport proteins
![Page 6: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/6.jpg)
2.3 Hydration of ions influences their flux through transmembrane pores
• Salts dissolved in water form hydrated ions.
• The hydrophobicity of lipid bilayers is a barrier to movement of hydrated ions across cell membranes.
![Page 7: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/7.jpg)
• By catalyzing the partial dehydration of ions, ion channels allow for the rapid and selective transport of ions across membranes.
• Dehydration of ions costs energy, whereas hydration of ions frees energy.
2.3 Hydration of ions influences their flux through transmembrane pores
![Page 8: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/8.jpg)
2.4 Electrochemical gradients across the cell membrane generate the membrane
potential
• The membrane potential across a cell membrane is due to:– an electrochemical gradient across a membrane – a membrane that is selectively permeable to ions
![Page 9: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/9.jpg)
• The Nernst equation is used to calculate the membrane potential as a function of ion concentrations.
• E: equilibrium potential (volts)• R: the gas constant (2 cal mol–1 K–1)• T: absolute temperature (K; 37°C = 307.5 °K)• z: the ion’s valence (electric charge)• F: Faraday’s constant (2.3 104 cal volt–1 mol–1)• [X]A: concentration of free ion X in compartment A• [X]B: concentration of free ion X in compartment B
2.4 Electrochemical gradients across the cell membrane generate the membrane potential
![Page 10: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/10.jpg)
• Cells maintain a negative resting membrane potential with the inside of the cell slightly more negative than the outside.
• The membrane potential is a prerequisite for electrical signals and for directed ion movement across cellular membranes.
2.4 Electrochemical gradients across the cell membrane generate the membrane potential
![Page 11: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/11.jpg)
2.5 K+ channels catalyze selective and rapid ion permeation
• K+ channels function as water-filled pores that catalyze the selective and rapid transport of K+ ions.
• A K+ channel is a complex of four identical subunits, each of which contributes to the pore.
![Page 12: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/12.jpg)
• The selectivity filter of K+ channels is an evolutionarily conserved structure.
• The K+ channel selectivity filter catalyzes dehydration of ions, which:– confers specificity – speeds up ion permeation
2.5 K+ channels catalyze selective and rapid ion permeation
![Page 13: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/13.jpg)
2.6 Different K+ channels use a similar gate coupled to different activating or inactivating
mechanisms• Gating is an essential property of ion
channels.
• Different gating mechanisms define functional classes of K+ channels.
![Page 14: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/14.jpg)
• The K+ channel gate is distinct from the selectivity filter.
• K+ channels are regulated by the membrane potential.
2.6 Different K+ channels use a similar gate coupled to different activating or inactivating mechanisms.
![Page 15: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/15.jpg)
2.7 Voltage-dependent Na+ channels are activated by membrane depolarization and
translate electrical signals• The inwardly directed Na+ gradient maintained by the
Na+/K+-ATPase is required for the function of Na+ channels.
![Page 16: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/16.jpg)
• Electrical signals at the cell membrane activate voltage-dependent Na+ channels.
• The pore of voltage-dependent Na+ channels is formed by one subunit, but its overall architecture is similar to that of 6TM/1P K+ channels.
• Voltage-dependent Na+ channels are inactivated by specific hydrophobic residues that block the pore.
2.7 Voltage-dependent Na+ channels are activated by membrane depolarization and translate electrical signals
![Page 17: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/17.jpg)
2.8 Epithelial Na+ channels regulate Na+ homeostasis
• The epithelial Na+ channel/degenerin family of ion channels is diverse.
• The epithelial Na+ channels and Na+/K+-ATPase function together to direct Na+ transport through epithelial cell layers.
• The ENaC selectivity filter is similar to the K+ channel selectivity filter.
![Page 18: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/18.jpg)
2.9 Plasma membrane Ca2+ channels activate intracellular functions
• Cell surface Ca2+ channels translate membrane signals into intracellular Ca2+ signals.
![Page 19: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/19.jpg)
• Voltage-dependent Ca2+ channels are asymmetric protein complexes of five different subunits.
• The α1 subunit of voltage-dependent Ca2+ channels forms the pore and contains pore loop structures similar to K+ channels.
2.9 Plasma membrane Ca2+ channels activate intracellular functions
![Page 20: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/20.jpg)
• The Ca2+ channel selectivity filter forms an electrostatic trap.
• Ca2+ channels are stabilized in the closed state by channel blockers.
2.9 Plasma membrane Ca2+ channels activate intracellular functions
![Page 21: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/21.jpg)
2.10 Cl– channels serve diverse biological functions
• Cl– channels are anion channels that serve a variety of physiological functions.
• Cl– channels use an antiparallel subunit architecture to establish selectivity.
![Page 22: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/22.jpg)
• Selective conduction and gating are structurally coupled in Cl– channels.
• K+ channels and Cl– channels use different mechanisms of gating and selectivity.
2.10 Cl– channels serve diverse biological functions
![Page 23: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/23.jpg)
2.11 Selective water transport occurs through aquaporin channels
• Aquaporins allow rapid and selective water transport across cell membranes.
• Aquaporins are tetramers of four identical subunits, with each subunit forming a pore.
![Page 24: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/24.jpg)
• The aquaporin selectivity filter has three major features that confer a high degree of selectivity for water:– size restriction– electrostatic repulsion– water dipole orientation
2.11 Selective water transport occurs through aquaporin channels
![Page 25: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/25.jpg)
2.12 Action potentials are electrical signals that depend on several types of ion
channels• Action potentials enable rapid communication
between cells.
• Na+, K+, and Ca2+ currents are key elements of action potentials.
• Membrane depolarization is mediated by the flow of Na+ ions into cells through voltage-dependent Na+ channels.
![Page 26: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/26.jpg)
• Repolarization is shaped by transport of K+ ions through several different types of K+ channels.
• The electrical activity of organs can be measured as the sum of action potential vectors.
• Alterations of the action potential can predispose for arrhythmias or epilepsy.
2.12 Action potentials are electrical signals that depend on several types of ion channels
![Page 27: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/27.jpg)
2.13 Cardiac and skeletal muscles are activated by excitation-contraction coupling
• The process of excitation-contraction coupling, which is initiated by membrane depolarization, controls muscle contraction.
• Ryanodine receptors and inositol 1,4,5-trisphosphate receptors are Ca2+ channels.– Ca2+ ions are released from intracellular stores into
the cytosol through them.
![Page 28: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/28.jpg)
• Intracellular Ca2+ release through ryanodine receptors in the sarcoplasmic reticulum membrane stimulates contraction of the myofilaments.
• Several different types of Ca2+ transport proteins, including the Na+/Ca2+-exchanger and Ca2+-ATPase are important for – decreasing the cytosolic Ca2+ concentration – controlling muscle relaxation
2.13 Cardiac and skeletal muscles are activated by excitation-contraction coupling
![Page 29: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/29.jpg)
2.14 Some glucose transporters are uniporters
• To cross the blood-brain barrier, glucose is transported across endothelial cells of small blood vessels into astrocytes.
![Page 30: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/30.jpg)
• Glucose transporters are uniporters that transport glucose down its concentration gradient.
• Glucose transporters undergo conformational changes that result in a reorientation of their substrate binding sites across membranes.
2.14 Some glucose transporters are uniporters
![Page 31: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/31.jpg)
2.15 Symporters and antiporters mediate coupled transport
• Bacterial lactose permease functions as a symporter.– It couples lactose and proton transport across the
cytoplasmic membrane.
• Lactose permease uses the electrochemical H+ gradient to drive lactose accumulation inside cells.
• Lactose permease can also use lactose gradients to create proton gradients across the cytoplasmic membrane.
![Page 32: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/32.jpg)
• The mechanism of transport by lactose permease likely involves inward and outward configurations.– They allow substrates to:
• bind on one side of the membrane and to • be released on the other side
• The bacterial glycerol-3-phosphate transporter is an antiporter that is structurally related to lactose permease.
2.15 Symporters and antiporters mediate coupled transport
![Page 33: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/33.jpg)
2.16 The transmembrane Na+ gradient is essential for the function of many
transporters• The plasma membrane Na+ gradient is maintained
by the action of the Na+/K+-ATPase.
• The energy released by movement of Na+ down its electrochemical gradient is coupled to the transport of a variety of substrates.
• The Na+/Ca2+-exchanger is the major transport mechanism for removal of Ca2+ from the cytosol of excitable cells.
![Page 34: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/34.jpg)
• The gastrointestinal tract absorbs sugar through the Na+/glucose transporter.
• The Na+/K+/Cl–-cotransporter regulates intracellular Cl– concentrations.
• Na+/Mg2+-exchangers transport Mg2+ out of cells.
2.16 The transmembrane Na+ gradient is essential for the function of many transporters
![Page 35: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/35.jpg)
2.17 Some Na+ transporters regulate cytosolic or extracellular pH
• Na+/H+ exchange controls intracellular acid and cell volume homeostasis.
• The net effect of Na+/HCO3–-cotransporters is to remove
acid by directed transport of HCO3–.
![Page 36: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/36.jpg)
2.18 The Ca2+-ATPase pumps Ca2+ into intracellular storage compartments
• Ca2+-ATPases undergo a reaction cycle involving two major conformations, similar to that of Na+/K+-ATPases.
• Phosphorylation of Ca2+-ATPase subunits drives:– conformational changes– translocation of Ca2+ ions across the membrane
![Page 37: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/37.jpg)
2.19 The Na+/K+-ATPase maintains the plasma membrane Na+ and K+ gradients
• The Na+/K+-ATPase is a P-type ATPase that is similar to the Ca2+-ATPase and the H+-ATPase.
• The Na+/K+-ATPase maintains the Na+ and K+ gradients across the plasma membrane.
• The plasma membrane Na+/K+-ATPase is electrogenic: – it transports three Na+ ions out of the cell for every two K+
ions it transports into the cell.
![Page 38: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/38.jpg)
• The reaction cycle for Na+/K+-ATPase is described by the Post-Albers scheme.– It proposes that the enzyme cycles between two
fundamental conformations.
2.19 The Na+/K+-ATPase maintains the plasma membrane Na+ and K+ gradients
![Page 39: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/39.jpg)
2.20 The F1Fo-ATP synthase couples H+ movement to ATP synthesis or hydrolysis
• The F1Fo-ATP synthase is a key enzyme in oxidative phosphorylation.
• The F1Fo-ATP synthase is a multisubunit molecular motor.– It couples the energy released by movement of protons
down their electrochemical gradient to ATP synthesis.
![Page 40: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/40.jpg)
2.21 H+-ATPases transport protons out of the cytosol
• Proton concentrations affect many cellular functions.
• Intracellular compartments are acidified by the action of V-ATPases.
• V-ATPases are proton pumps that consist of multiple subunits, with a structure similar to F1Fo-ATP synthases.
![Page 41: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/41.jpg)
• V-ATPases in the plasma membrane serve specialized functions in:– acidification of extracellular fluids– regulation of cytosolic pH
2.21 H+-ATPases transport protons out of the cytosol
![Page 42: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/42.jpg)
Supplement: Most K+ channels undergo rectification
• Inward rectification occurs through voltage-dependent blocking of the pore.
![Page 43: Chapter 2](https://reader030.fdocuments.us/reader030/viewer/2022032710/56815c9c550346895dcaa727/html5/thumbnails/43.jpg)
Supplement: Mutations in an anion channel cause cystic fibrosis
• Cystic fibrosis is caused by mutations in the gene encoding the CFTR channel.
• CFTR is an anion channel that can transport either Cl– or HCO3
–.
• Defective secretory function in cystic fibrosis affects numerous organs.