PL1003 Cell Membrane Proteins Lecture Notes PDF

PH1131 Cell Membranes (2) Stuart Cruickshank  Mammalian Cell Pla s m a m e m b r a ne S m o o t h e nd o pla s m ic r e t ic ulum He t e r o c h r o m a t in Ro ug h e nd o pla s m ic...

PH1131 Cell Membranes (2) Stuart Cruickshank  Mammalian Cell Pla s m a m e m b r a ne S m o o t h e nd o pla s m ic r e t ic ulum He t e r o c h r o m a t in Ro ug h e nd o pla s m ic r e t ic ulum Nucleus Nuc le a r po r e Rib o s o m e s Nuc le o lus Cy t o s ke le t a l Ce nt r io le e le m e nt s Mit o c h o nd r ia Ly s o s o m e s Go lg i a ppa r a t us  Plasma membrane Lipid Bilayer extracellular hydrophilic phospholipid head hydrophobic glycolipid core cholesterol hydrophilic intracellular Lipid bilayer essentially impermeant barrier to water, ions and hydrophilic molecules (permeant to hydrophobic materials and gases) But plasma membranes contain membrane proteins  transport water, ions and hydrophilic molecules  Transport across the plasma membrane Hydrophilic uncharged molecules and ions require membrane transport proteins to cross the plasma membrane Two classes of transport protein: ion channel proteins carrier proteins closed open  Characteristics of transport proteins Ion channels Form aqueous pores which span membrane Move inorganic ions across membrane (Na+, K+, Cl-) High capacity for transport (108 ions/second) Highly selective for specific ion species Carrier proteins Bind specific substances (eg glucose, amino acids, ions) then undergo conformational change to deliver transported molecule across membrane Lower transport capacity than channels (102-103 molecules/second) Highly selective (including stereoselectivity)  Principal types of carrier protein Transported molecule/ion Co-transported ion Counter-transported ion Uniport Symport Antiport  Ionic gradient Extracellular Na+ 5 mM K+ Na+ Na+ 145 mM Na+ Na + Na+ K+ Na+ Na+ Na+ Na + Intracellular Na+ 150 mM K Na+ K+ 12 mM Na+ K+ Na+ K+ Na+ K+ K+ K+ Na+ K + K + K+ K + Na+ Na+ K + K+ Na+ Na + K+ K+ K+ Na+ Na+ K+ Na+ Membrane Na+ Na + K+ Na+  Excitable cells Ion movements Intracellular Membrane Extracellular 150 mM K+ 5 mM K+ 12 mM Na+ 145 mM Na+ Ions will move down their concentration gradients K+ K+ out of the cell (efflux) Na+ into the cell (influx)  Resting membrane potential Excitable cell at rest Intracellular Membrane Extracellular Membrane spanning proteins: K+ channels and Na+ channels 150 mM K+ 5 mM K+ 12 mM Na+ X 145 mM Na+ At rest the membrane is selectively permeable to K+  RMP: Excitable cell at rest START K+ EFFLUX K+ A- A- K+ K+ Development of Negative charge K+ A- A- on inside of the membrane A- A- K+ K+ K+ K+ A- A-  RMP: at rest Potassium ions move out of the cell down concentration gradient: negative charge on inside of cell membrane 150 mM K+ 5 mM K+ EK A- BUT + BUT negative charge potassium A- + attracts positive + equilibrium A- potassium ions back + potential A- into the cell A- + -80mV A- + Where these electro-chemical forces are in balance is know as the IONIC EQUILIBRIUM POTENTIAL E ion  Basis of the membrane potential Selective permeability Movement of charge sets up electrical gradient, opposing concentration gradient Point where the forces balance termed equilibrium potential EK = -80mV ENa = +30mV At rest, membrane is ~100 times more permeable to K+ than Na+ As a result, resting membrane potential is close to EK  Active ion transporters or pumps Membrane also contains active pumps. The sodium -potassium pump (Na+K+ ATP’ase) which pumps Na+ out of the cell and K+ in with a ratio of 3 Na+ out :2 K+ in. This is termed electrogenic Helps to maintain the ionic gradients and in neurones 50- 70% of ATP utilised is by this pump In neurones electrogenic pump also contributes to resting membrane potential (~ -10mV) NB not necessarily true of all cells.  The Na+/K+ ATPase Maintenance of low [Na+]i and high [K+]i requires ATP All mammalian cells (so far!) express Na+/K+ ATPase (sodium pump) in plasma membrane Antiport carrier protein, uses ATP hydrolysis to pump 3 Na+ out of cell in exchange for 2 K+ into cell Inside cell negatively charged with respect to outside  membrane potential 2K+ Extracellular + Intracellular - ATP ADP + Pi 3Na+  Changing Membrane Potential The charge separation across the membrane, and therefore the resting membrane potential, is disturbed whenever there is a net flux of ions into or out of the cell. A reduction of the charge separation is called depolarization An increase in charge separation is called hyperpolarization  Ion composition of intracellular & extracellular fluid (muscle) Ion [Extracellular] [Intracellular] (mmol.l-1) (mmol.l-1) Na+ 145 12 K+ 5 150 Ca2+ 1.8 ~0.0001 Cl- 114 3 HCO3- 31 10 This table is VER Y IMPORTANT!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! [Na]e >> [Na]i  Na moves into cells [K]e>> [Ca]i  Ca moves into cells