Cellular Neurphysilgy Membrane Inic Gradients Fluid-msaic mdel f plasma membrane: lipid bilayer separating intracellular and extracellular fluids Biplar phsphlipids Hydrphilic head grups and hydrphbic tails (interact with each ther via Van der Waals) Self-assembling and stable Barrier t large, charged plar mlecules Can be mdified by the additin f: Transmembrane prteins such as channels, transprters, receptrs (prvide a means fr mlecules and ins t pass int the cell) Membrane-attached prteins such as cytskeletn-linking prteins Specialised lipids and glyclipids Channels and transprters which selectively mdify permeability f membrane Intrinsic prteins g thrugh the whle membrane while extrinsic are just n the tp r bttm Cncentratin gradients and diffusin Cells set up cncentratin gradients which prduce frce t allw mlecules/ins t mve Osmsis: high cnc. à lw cnc. Membrane transprt: fr substances that cannt diffuse acrss the lipid bilayer there is: Active transprt membrane prteins use energy t frce a substance e.g. ins up the cnc. gradient (i.e. make it mre cncentrated) Primary active transprter prteins use ATP as energy e.g. Na + /K + pump 1. There are 3 binding sites fr Na + ins 2. ATP harvests a P mlecule that is attached t the transprter 3. Energy transferred makes it swivel t expse the ECF side 4. Na + ins are pushed ut f the binding site 5. 2 new binding sites (different shapes) pen fr K + ins 6. P grup is cleaved ff which triggers the transprter t swivel back t the ICF side 7. K + ins are released
Secndary active transprter prteins use the diffusin energy f pre-existing cncentratin gradients as energy e.g. Na + /glucse transprter (linked t the Na + /K + pump as the glucse imprt is driven by the Na + cnc. gradient which is in turn maintained by the Na + /K + pump) 1. Na + /K + ctransprter helps glucse pass thrugh int gut 2. When bth sites are ccupied by glucse and Na + it swivels withut needing ATP fr energy Facilitated diffusin facilitate a substance diffusing acrss the membrane mlecule by mlecule Mlecules t be transprted enter the transprter prtein then upn binding it changes its cnfrmatin s that mlecules can be released int the ther side Facilitated diffusin is driven by the chemical driving frce acting n the substance Diffusin channels e.g. water channels and in channels Electrical Ptential Acrss Membranes Cells have an electrical ptential acrss their membrane which can be measured acrss the plasma membrane f a mtr neurn (resting membrane ptential is apprx. -60milliV) Cncentratins f ins changes between the plasma, intracellular fluid and interstitial fluid therefre there is a high cncentratin gradient which allws Na + int the cell and K + ut f the cell à chemical driving frce required fr diffusin Extracellular fluid (cnductr) à Na + and Cl - ins Lipid bilayer (insulatr) Cytplasm (cnductr) à K + ins and rganic anins NOTE: rganic anins are t big t pass thrugh the in channels as the membrane is selectively permeable Only a tiny imbalance f anins vs. catins is required t generate physilgical membrane ptentials (nly ne extra anin in 200 000 catins needed fr a ptential difference t be generated) T change a ptential, a diffusin frce drives catins r anins acrss the membrane There are fur types f in channels which permit inic currents: Nn-gated (leakage) channels: permeable t Na + and K + Vltage gated: permeable t Na +, K +, Cl - and Ca 2+ Ligand gated: permeable t Na +, K +, Cl - and Ca 2+ Electrical frces: in a resting (nn-signalling) neurn, the inside is mre negative than the utside therefre the resting membrane ptential is negative/plarised à RESTING MEMBRANE POTENTIAL Vectr diagrams: demnstrate the frces acting n ins acrss a membrane
When ne K + mves ut thrugh a nn-gated K selective channel by a chemical driving frce, an electrical driving frce ppsing it is created (less than the chemical but still present) and the membrane becmes plarised (mre negative n the inside) Onging diffusin f K + wuld eventually result in an equilibrium ptential being reached Electrical driving frce = chemical driving frce = equilibrium ptential/nernst ptential Prcess is same fr Na + ins but chemical frce is inwards and electrical is utwards Nernst Ptential: depends n the cnc. gradient f the cell in questin! " = $% ln ] / &' (["- ) [" - ] 0 T = temp. in Kelvin, R = Gas Cnstant, F = Faraday cnstant, Z = valence f the in Inic currents (Amps): prduce changes in the membrane ptential The rate f in mvement depends n the driving frces n the in and n the permeability f the membrane t that in Relative permeability f the membrane t Na + vs. K + is crucial in determining NET mvement f charge Leakage currents buffer the resting membrane ptential If V m were t rise suddenly due t a synaptic input, the reduced electrical driving frce autmatically cmpensates by increasing the utward flw f K and reducing the inward leakage f Na If V m were t drp suddenly, the increased electrical frce drives mre Na ins in thrugh leakage channels t bring it back t its natural resting value The net frce n each in is the sum f the chemical and electrical frces (nte the electrical driving frce changes every time the membrane ptential changes) Relative permeability: When the membrane is permeable nly t K +, V m will be the Nernst ptential fr K + and vice versa fr Na + When the membrane is permeable t bth K + and Na +, then E K < V m < E Na (the resting membrane is abut 20 times mre permeable t K + than t Na + Gldman Equatin: understanding influences f ins in maintaining the resting membrane ptential Actin Ptentials Neurns and ther excitable cells prduce actin ptentials (APs) when they receive electrical r chemical stimulatin Excitatry inputs raise the membrane ptential (deplarisatin) s there is a less negative ptential i.e. the dendrites are less negative than the cell bdy Electrical signalling gets weaker the further it travels à a need fr an amplificatin system The actual numbers f ins mving during each AP are very small and hence cell in cncentratins in the cell as a whle are nt altered measurably Deplarisatin is initiated by the pening f ligand gated catin channels at an excitatry synapse A rise in Na + ins t the inside means the ptential difference gets clser t zer (i.e. the difference between inside and utside is nt as significant) Hdgkin Cycle: a psitive feedback cycle resulting in a prgressive increase in the permeability f the membrane Stimulus deplarisatin pens a small amunt f Na + channels The inward current thrugh these channels further raises (deplarises) the membrane channel Mre channels pen s mre current mves thrugh s mre pen etc. Vltage gated Na + channels can exist in three states: Clsed: mst f the time when the membrane is plarised, selectively permeable t Na +,
Open: when the membrane deplarises Inactivated (n ins pass thrugh) à stay inactivated as lng as the membrane is deplarised Vltage gates and inactivatin gates Vltage gated Na + channels stay inactivated fr a fractin f a millisecnd after the AP preventing a secnd AP. Vltage-gated K + channels: Mstly clsed when the membrane is plarised and begin t pen as the membrane deplarises D nt inactivate Slwer than activatin gate f Na + channels (hence the flatter graph shape abve) A stimulus will pen sme vltage gated Na + channels and the Hdgkin cycle will begin but as the cell rapidly deplarises the Na + channels will begin t inactivate and the K + channels will begin t pen and the cell will replarise During a perid f reduced excitability/hyperplarisatin (just after an actin ptential) it is less likely that an actin ptential will be triggered K + channels remain pen fr a bit lnger, allwing excess K + ut and hyperplarising the cell Infrmatin is encded by AP frequency: when they becme deplarised, neurns fire hundreds f APs and the frequency f these encdes the intensity f the sensatin r instructin Rle f Na + /K + pump: gives a cncentratin gradient BUT is slw t build up this gradient Actin Ptential Prpagatin There are limitatins n signal transmissin f an AP in axns due t electrical prperties The membrane has electrical prperties that slw the spread f charges in membrane ptential 1. Electrical capacitance (the tendency f the lipid bilayer t stre charges) 2. Leakage channels ut f the membrane (the ability t allw charge acrss fr a given area f membrane) 3. The axplasm (cytplasm in the axn) is narrw and has resistance which impedes the deplarising current dwn the membrane (i.e. less ins can pass thrugh) Prpgatin alng an axn: 1. Ins enter s ptential ges frm e.g. -60mV t -40mV 2. Charge spreads ut thrugh leakage channels and disperses acrss the axn t discharge stred charges s the membrane ptential respnse declines with distance V m decreases slwly as it takes time fr the charge t rebuild back t its strage level hence the tendency f the membrane t stre charge. This decrease in V m means we can t send electrical signals ver lnger distances.
Cntinuus Prpagatin (ccurs alng an individual nde) The AP starts at the axn hillck (where the density f vltage gated Na + channels is high) and in nn-myelinated nerves it then prpagates cntinuusly alng the axns by sequentially activating Na + channels in adjining segments f axn The pen Na + channel generates excess + charge which deplarises the next part f the membrane (due t the spread f charge) s the next set f Na + channels pen and the previus nes becme inactivated (s the AP desn t g backwards) then clsed Therefre the deplarised bit f membrane spreads like a wave Saltatry Prpagatin (ccurs ver a whle neurn) Allws fr faster prpagatin withut the signal deterirating due t the presence f myelin ndes (Schwann cells wrapped arund axns) as they act as an amplificatin system at regular intervals alng the axn The thick myelin insulatin allws the current t spread further and faster Vltage-gated Na + channels are cncentrated in the axn hillck and ndes making these areas sensitive t deplarisatin, then the Hdgkin Cycle bsts the signal at the ndes allwing it t reach the next nde as an electrical current withut V m deterirating dwn The Myelin sheath With: sufficient vltage at next nde t initiate Hdgkin Cycle When myelinated: High-resistance wall minimising cntact with the extracellular fluid t prevent in flw ut f the cytplasm Channel pening slws cnductin s slwing dwn will nly ccur the ndes à faster current Withut: vltage diminishes befre reaching the next nde and currents leak ut the leakage channels When demyelinated: Increased permeability f membrane t ins Increased membrane capacitance à increased charge strage à slwer spread f deplarisatin Reduced membrane electrical resistance à decrease in current flw à slwer prpagatin f AP signal Channel pening slws cnductin s slwing dwn will ccur all alng the membrane Synaptic Transmissin Chemical Synaptic Transmissin Fast synaptic transmissin - Neurtransmitter chemical binds t and pens a specific type f ligand-gated in channel - Rapid (ms) respnse due t diffusin f ins - Inward and utward currents summate Neurmdulatin - Neurmdulatr chemical binds receptr t activate secnd messengers in pstsynaptic cell - Respnse takes secnds r minutes - Mdulates neurn excitability