Synapses and neurotransmission lecture.pptx

Life Sciences Membrane potential, Synapses & Neurotransmit ters School of Medical Sciences Dr. Ramin Farahani Acknowledgments Dr Jinlong Gao, Dr Belal Chami The University of Sydney Page 1  Learning Objectives - List the excitable cells in human body - Describe the basis of electrical...

Life Sciences Membrane potential, Synapses & Neurotransmit ters School of Medical Sciences Dr. Ramin Farahani Acknowledgments Dr Jinlong Gao, Dr Belal Chami The University of Sydney Page 1  Learning Objectives - List the excitable cells in human body - Describe the basis of electrical excitability and the membrane potential - Explain the generation of action potentials - Understand the effects of nerve diameter and myelination on conductance - Define synapse and neurotransmitter - Understand the principle of anaesthetic function from a physiological point of view The University of Page 2 Sydney  Introduc tion The brain sends a message to certain muscles of your hand. They contract and the hand moves. What is this message? How does it travel so quickly? The University of Page 3 Sydney Excitable cells - Cells that can be electrically excited resulting in the generation of action potentials - Neurons - Muscle cells (skeletal, cardiac, smooth) - Some endocrine cells (e.g. insulin secreting pancreatic β-cells - Action potential - Brief reversal of electric polarization of the cell membrane - Controlled by movement of ions across cell membrane The University of Page 4 Sydney  Nerve Impulses (Action –potential) Difference in electrical charge across plasma membrane – Fastest process in the cell – Energy efficient: apply chemical gradients that already exist – Dependable over long distance – Communication between cells – Electrical signal converted to chemical signal  neurotransmitters The University of Page 5 Sydney  Membrane Potential – Definition: Electrical potential difference between the inside of the cell and the surrounding extracellular fluid – Present in all cells – Especially important in nerve and muscles cells – Function - Code and transmit information (sensory and motor) The University of Page 6 Sydney  Resting Membrane Potential – The cell is in the “rest” state – Determined by concentration gradients of ions across membrane – Neuron: -70 mV (polarised) – The inside of the cell is negative with respect to the surrounding extracellular fluid – The degree of positivity inside the cell is lower than the outside The University of Page 7 Sydney  How is membrane potential generated? & How does a cell maintain the electrical potential? The University of Page 8 Sydney  Resting Membrane –Potential Phospholipid bilayer is an isolator – Ions are not soluble in the lipid bilayer – Cell membrane exhibit selective permeability – Cell can be deemed as a capacitor – The excitable cells are able to discharge – signal – action potential The University of Page 9 Sydney Review: Membrane Transport Proteins – Ion Channels – Water filled pores across the membrane – Facilitated diffusion – Specific – Gated – open or closed in response to local changes – “Leak” channels (two pore domain potassium channel) – Ligand-gated: signal molecule, can be external (e.g. neurotransmitter) or internal (Ca2+, cAMP, lipids, etc.) – Voltage-gated: alterations in membrane potentials The University of Page Sydney 10 Review: Membrane Transport – Ion Pumps Proteins – Use energy – Active transport against concentration gradient – Catalyse the hydrolysis of ATP to ADP – E.g. Na+/K+-ATPase (move 3 Na+ out and 2 K+ into the cell at the same time) – Outcome: the concentration of K+ inside the cell becomes higher than that outside, and the Na+ is lower than that outside. The University of Page Sydney 11  Generation of Resting Membrane Potential – Ion – atom or molecule in which the total number of electrons is not equal to the total number of protons – charged – Cation (+): Na+, K+, etc – Anion (-): Cl-, proteins, etc – Much higher levels of Na+ outside of cells – K+ much higher inside cell – Facilitated by Na+/K+ pump The University of Page Sydney 12  Generation of Resting Membrane Potentials – Separation of ions across the membrane – Cell membrane has different permeability to ions – 3Na+/2K+ pump – Unequal distribution of ions – Formation of concentration gradient between inside and outside of the cell The University of Page Sydney 12 Generation of Resting Membrane Potentials – Other channels that specifically move K+ and Na+ ions – Many more K+ channels than Na+ (100x more) – K+ continues to diffuse out of cell until electrical potential is equal – Two forces act on K+: Electrical potential repel the – Concentration gradient  move K+ out diffusion – Electrical potential  pull K+ in K+ The University of Concentration gradient Page Sydney Diffusion through potassium channels 14  Action – Potential Needs a stimulus – other neuron or sensors – The dynamic changes in the membrane potential in response to the stimulus – Also called “nerve impulse” – a very brief electrical impulse that travels along the nerve fibre (axon) – After the action potential, cell membrane goes back to its resting state The University of Page Sydney 15 Generation of Action Potential – Ligand-gated channels open with stimulation (chemical or physical) – Inflow of cations (i.e. Na+ and Ca2+) and lowers the membrane potential – Open the voltage-gated Na+ channels – Membrane is ~600 times more permeable to Na+ – Local depolarization of cell membrane – Membrane potential becomes less negative and more positive (+30mV) - Spread of depolarization down the axon - Depolarization decays with distance The University of Page Sydney 16 Voltage gated Na+ channel – Ion selectivity – Na+ only – Gate controlled by a voltage sensor which responds to the level of the membrane potential – Normally closed and open only when prompted by gating agent – voltage above the threshold The University of Page Sydney 17 The University of Sydney Page 17 Action Potential › Phase I – Depolarisation › Phase II – Repolarisation - Inactivation of voltage-gated Na+ channels after 0.5-1 msec - Opening of voltage-gated K+ channels and K+ efflux and starts to repolarise the cell › Phase III – Hyperpolarisation and back to RMP - Increased K+ permeability - The closure of K+ channels is a delayed process - Voltage-gated Na+ channels return to active but closed status - The Na+/K+ pump returns the membrane potential to resting state The University of Page Sydney 19 Propagation of Action Potential – Sequential opening, inactivation and closing of Na+ and K+ voltage-gated channels – Cause respectively depolarisation and repolarisation of the cell membrane – After an action potential there is a refractory period when the membrane is hyperpolarized and not as excitable – one direction of current flow The University of Page Sydney 20 Speed of Action Potential Propagation – Axon resistance – Larger diameter less resistance – Myelin provides additional isolation on the axon, maintain the initial stimulus – Action potentials only produced in the exposed spaces of Ranvier’s nodes – Current spreads under myelin – Unmyelinated nerve, current leak slows The University of Page conduction Sydney 21 Synaptic Signalling – A special case of paracrine signalling – A special structure is involved – Synapse (between the cell originating and the cell receiving the signal) – Only occurs between cells with the synapse – Communication between neurons or between neuron and effectors (i.e. muscle cells) The University of Page Sydney 22  Synaptic neurotransmission Electrical Electrical Chemical synapse synapses s synapses The University of Page Sydney 23  Neurotransm –itters NTs – biological active chemicals that transmit signals from a neuron to another neuron or target cell across a synapse – Excitatory NTs – Acetylcholine (Ach), Noradrenaline (NA), Glutamate etc – Influx of Na+ - Depolarisation – Action potential – Inhibitory NTs – γ-aminobutyric acid (GABA), Glycine – Influx of Cl- - TheHyperpolarisation University of – Difficult Page Sydney 24 to reach threshold Why do we need to know about the action potential a n d neurotransmitters as a health profession? The University of Page Sydney 25  Pain Management An operator extracting a tooth, unidentified painter, after Theodor Rombbouts (1597-1637) British Dental Journal 196, 502 - 503 (2004) The University of Page Sydney 26 Tooth Pain › Aδ fibre – myelinated, thicker - Fast transmitting information - Sharp pain, well localised › C fibre – unmyelinated, thinner - Slow pain, burning sensation, lingering pain - Chronic pain, poorly localized pain The University of Page Sydney 27 Local Anaesthesia › Local anaesthetic – A drug which reversibly prevents transmission of the nerve impulse in the region to which it is applied, without affecting consciousness › Lignocaine binds to voltage-gated Na+ channels in the peripheral nerve cell membrane and blocks the influx of Na+ The University of Page Sydney 28 Recap Question Which of the following conditions could initiate the cell depolarization? – A)more K+ diffuse into the cell than Na+ diffuse out of it. – B)more K+ diffuse out of the cell than Na+ diffuse into it. – C)more Na+ diffuse into the cell than K+ diffuse out of it. – D)more Na+ diffuse out of the cell than K+ diffuse into it. – E) both Na+ and K+ diffuse into the cell. The University of Page Sydney 29