Module 1: Membrane Structure & Function

Transcription

1 Module 1: Membrane Structure & Function Concept 7.1 Cellular Membrane Structure Fluid mosaic of lipids & proteins o Phospholipids abundant, amphipathic o Proteins embedded o Cholesterol Fluidity unsaturated hydrocarbon tails with kinks Viscosity saturated hydrocarbon tails Cholesterol o Acts as buffer when temperature changes by controlling fluidity o Cold limits viscosity o Hot limits fluidity o Keeps structure Membrane Proteins N-Terminus C-Terminus Sequence of AA determine how they arrange themselves function Charged side chains interact with water, thus face to extracellular side Functions Transport Enzymatic activity Signal transduction Cell-cell recognition Intercellular joining Attachment to the cytoskeleton & ECM Concept 7.2: Membrane Structure results in Selective Permeability Some permeability to water molecules & other small, uncharged molecules like O2 & CO2 Lipid bilayers are NOT permeable to: o Ions o Small hydrophilic molecules like glucose o Macromolecules like proteins & RNA Concept 7.3: Passive Transport Diffusion of a substance across a membrane with no energy investment

2 Diffusion: With time, due to random motion, molecules become equally distributed i.e. to eliminate concentration gradients provided molecules can cross the membrane Osmosis: Diffusion of water through a selectively permeable membrane into another aqueous compartment containing solute at a higher conc. Tonicity: ability of a solution to cause a cell to either gain or lose order o Isotonic: solute conc. is the same as that inside the cell; no net water movement o Hypertonic: solute conc. is greater than inside the cell; cell loses water o Hypotonic: solute conc. is less that inside the cell; cell gains water o 1 mol = 1 osmol 1 mol/l = 1 osmol/l ANIMAL CELL: best in isotonic env. unless special adaptations that offset osmotic uptake/loss of water PLANT CELL: turgid (firm) thus generally healthiest in hypotonic environment where the uptake of water is eventually balanced by the wall pushing back on the cell Facilitated Diffusion: Transport proteins speed the passive movement of molecules across the plasma membrane Channel proteins provide corridors that allow a specific molecule or ion to cross Channel proteins include: o Aquaporin s for facilitated diffusion of water o Ion channels that open or close in response to stimulus (gated channels) Concept 7.4: Active Transport Movement of a substance against a concentration gradient through energy investment (hydrolysis of ATP) Transport Proteins: Same as facilitated diffusion but molecule moves against conc. gradient Transport proteins allow passage of hydrophilic substances across the membrane, is specific for the substance it moves Channel proteins have hydrophilic channel that certain molecules or ions can use as a tunnel e.g. aquaporins (water) Carrier proteins bind to molecules & change shape to shuttle them across membrane Electrogenic pump is a transport protein that generates voltage across membrane o Sodium-potassium pump is the major electrogenic pump of animal cells AGAINST conc. gradient o Proton pump is the main electrogenic pump of plants, fungi & bacteria Cotransport: When active transport of a solute indirectly drives transport of another solute Plants commonly use H + gradient generated by proton pumps to drive active transport of nutrients into cell

3 Concept 7.5: Bulk Transport Movement of macromolecules into or out of the cell form of active transport Vesicle: Small structure within cell consisting of fluid enclosed by lipid bilayer membrane Endocytosis: Movement of materials into a cell via membranous vesicles Phagocytosis: Cells engulf large particles e.g. bacteria, cell debris & even intact cells Pinocytosis: Uptake of fluids or molecules into a cell by small vesicles cell drinking Receptor-mediated Endocytosis: Selective uptake of macromolecules that bind to cell surface receptors that concentrate in clathrin-coated pits Exocytosis: Movement of cells out of the cell via membranous vesicles Module 1: Cell Communication & Function Chapter Signalling Local Signalling Paracrine Signalling: A secreting cell acts on nearby target cells by discharging molecules of a local regulator (e.g. growth factor) into the extracellular fluid Synaptic Signalling: Electric signal along nerve cell triggers release of neurotransmitter molecules into synapse that diffuses across, stimulating the target cell Long-Distance Signalling Hormonal Signalling: Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells, travelling in the bloodstream 3 Stages of Cell-Signalling Reception Hormone/Ligand/Agonist act via receptors Hydrophilic signalling molecules binds to receptors doesn t need to enter cell Steriod receptors Signalling molecule can be hydrophobic (lipid soluble) simple diffusion travel in blood via carrier proteins molecule must bind to receptor inside cell move into nucleus, changing gene transcription Transduction Response Gene activation, enzyme stimulation, rearrange cytoskeleton

4 Plasma Membrane Receptors Ion channel receptors Na + channel opened by ligand e.g. nicotinic receptors fast neurotransmission G Protein-coupled receptors Largest known class of membrane receptors Each one function specific Responsible for all aspects of physiology & pharmacology o 50% of drugs target GPCRs 7 trans-membrane spaning regions (alpha helices) G Proteins: Specialised proteins that bind GTP & GDP Transduction Signalling molecule binds to extracellular receptor of GCPR Conformational change occurs & activates receptor triggers interaction with G protein HETEROTRIMERIC (3 distinct subunits) G-protein exchanges GDP for GTP on a-subunit a-subunit disassociates from β & γ and diffuses along membrane, binding to enzyme Signal is relayed Specific targets include enzymes that produce second messengers to regulate cell functions Signalling molecule (Ligand) departs as GTP hydrolysed to GDP G proteins remain active as long as GTP is joined to a-subunit As long as ligand is bound to GCPR, chain of events can happen repeatedly e.g. ADRENALINE binds to GPCR conformational change (GDP->GTP) a-subunit dissociates regulates Adenylyl cyclase ATP converted to camp second messenger camp activates PKA phosphorylation of proteins causes regulation of cell functions (increased heart rate, dilate blood vessels, glycogen glucose)

5 Tyrosine kinase linked receptors 1 Transmembrane domain Insulin receptors metabolism, cell growth & cell reproduction Tyrosine Receptor Kinase Linked Receptor becomes enzyme activator, activating kinases that transfer phosphate groups to proteins (PO4 -- ) Phosphorylation conformational change or enhance protein interaction activate or inactivate protein Intracellular Receptors Steroid receptors Lipid soluble hormone binds to receptor moves into nucleus attaches to DNA Gene transcription occurs new protein forms VERY SLOW Module 2: Neural Transmission Cells & Ions Concept 48.1: Neuron Structure & Organization reflects Function Direction of signal

6 Information Processing 3 stages in producing response Sensory Input Integration Motor Output Nerves Collection of neurons Glial Cells (Glia) Structural Integrity & normal function Astrocytes (star cells) o Star cells o CNS o Regulate extracellular concentration of ions & neurotransmitter o Supply nutrients from blood to neurons for energy o Formation of blood-brain barrier Oligodendrocytes (CNS) Schwann Cells (PNS) o Produce Myelin- fatty substance which wraps around axons & neurons o Essential for transmission of neural signals o Lipid membranes: insulator Concept 48.2: Ion Pumps & Channels Resting Membrane Potential: Inside of the membrane is NEGATIVE relative to the outside 3 Na + out and 2 K + in Membrane at rest has many open K + channels & few open Na + or Cl - channels Build-up of ve charge in neuron: limited by electrical gradient vs. chemical gradient of K + Equilibrium potential in neuron approx. -70mV PROCESS NOT DEPENDENT ON VOLTAGE-GATED ION CHANNELS Voltage-gated Ion Channel Ion channels that open due to voltage change depolarization/hyperpolarisation Membrane Potential: Voltage of inside of membrane relative to outside equilibrium Hyperpolarisation: Inside of membrane becomes more negative o Opening of voltage-gated K + channel K + flows out Depolarisation: Inside of membrane becomes more positive o Opening of voltage-gated Na + channels Na + flows in

7 Concept 48.3: Action Potentials are signals conducted by axons Action Potentials Generated at Axon Hillock Human neuron is at resting membrane potential of -70mV Diffusion of Na + & K + ions into and out of the cell is prevented by voltage-sensitive channels being closed Stimulated membrane causes Na + channels to open Na + diffuse into cells down conc. gradient, causing depolarisation in the rising phase o 3 Na + pumped out for every 2 K + pumped in by Na + /K + -ATPase electrogenic pump When membrane reaches threshold level, action potential arises, generating an impulse During delay inactive Na + voltage channels are closed & K + voltage channels open As K + leaves the cell the membrane become more negative, causing repolarisation in the falling phase o During falling phase, inactive Na + gates open, Na + cannot enter as activation gates are being reset Slow closure of the K + voltage channels cause membrane potential to undershoot i.e. more negative than rest When all K + channels close, membrane potential is restored to rest All or None Response Magnitude independent of strength of stimulus Na + continues to rush inside until action potential reaches peak & voltage-gated channels close If depolarisation is not great enough to reach peak, action potential & impulse is not produced Voltage-gated Na + & K + channels During depolarisation o Na + channels go from closed to open fast before going from open to closed it becomes inactive o K + channels go from closed to open slower Refractory Periods (RP) Voltage gated Na + channels inactivated during repolarisation and cannot re-open until closed Absolute RP (ARP): period when activation channels are open & no new AP can be generated Relative RP (RRP): period between resetting of activation channels & membrane returning to rest o Some Na + channels are closed again however some are open limits firing frequency o Allows AP to be generated but only if large stimulus applied as: > K + is flowing out making membrane potential more negative

8 o > When K + close membrane potential is at undershoot, thus more negative If activation channels not appropriately reset, rising phase of action potential is Speed of Impulses affected Axon Diameter: Larger diameter less resistance FASTER conduction speed Invertebrates: speeds vary from a few cm/s to 100m/s in giant squid axon Temperature: Any chemical reactions occurs faster at warmer temperatures Myelination: Myelin insulates axon membrane in vertebrated FASTER conduction speed Conduction speed is affected more by myelination than diameter Presynaptic Neuron Post Synaptic Neuron Presynaptic Neuron Effector Cell Concept 48.4: Neurons communicate with other cells at synapses Communication at Synapses In most cases AP s are not transmitted from neurons to other cells; info. is transmitted at synaptic terminals Electrical Synapses Occurs at gap junctions which allow electrical current to flow between neurons Synchronise activity of neurons responsible for certain rapid, unvarying behaviours o Electrical synapses associated with giant axons of squids & lobsters facilitate swift escapes from danger Chemical Synapses Makes up majority of Synapses Involves release of chemical neurotransmitter by presynaptic neuron Presynaptic neuron synthesis & packages neurotransmitter in membrane closed synaptic vesicles

9 Depolarisation via AP Voltage gated Ca 2+ channel opens calcium diffuses into cell binds to vesicles containing neurotransmitters vesicles bind to cell membrane neurotransmitter released EXOCYTOSIS Chemical Synaptic Transmission Direct Synaptic Transmission Neurotransmitter opens ion channels on postsynaptic membrane Action via ligand-gated ion channels Indirect Synaptic Transmission Neurotransmitter binds to receptor on postsynaptic membrane Activates signal transduction pathway Involves second messenger SLOWER Generation of Postsynaptic Potentials Ligand-gated ion channel (ionotropic receptor): Receptor protein that binds neurotransmitters Binding of neurotransmitter (receptor s ligand) opens channels & allows diffusion of specific ions This causes postsynaptic potential: a graded potential in postsynaptic cell At some synapses, permeability is to K + & Na + causing: o Excitatory Postsynaptic Potential (EPSP): depolarisation occurs at postsynaptic membrane At some synapses, permeability is to K + & Cl - causing: o Inhibitory Postsynaptic Potential (IPSP): hyperpolarisation occurs at postsynaptic membrane Summation of Postsynaptic Potentials Temporal Summation: Several consecutive EPSPs from same synapse Spatial Summation: Two or more EPSPs from different synapses Neurotransmitters Amino Acid Neurotransmitters GABA, Glycine depolarisation inhibitory Glutamate, Aspartate depolarisation excitory Amine Neurotransmitters Acetylcholine NS function including muscle stimulation, memory formation & learning Noradrenaline works on G-protein receptors Biogenic Amines: Have central role in various NS disorders by affecting sleep, mood, attention & learning o Dopamine: Lack of in brain Parkinson s disease

10 o Serotonin: Lack of depression Removal of Neurotransmitters from Synaptic Cleft Diffusion Broken down by enzymes Transporters recycle through selective uptake Taken up by astrocytes