Lecture 3-2 Changing Membrane Potentials PDF

MEMBRANES AND RECEPTORS SESSION 3 THE RESTING CELL MEMBRANE LECTURE 3.2 CHANGING MEMBRANE POTENTIALS Lecturer Dr. Safa Amir 1 References Ganong, W.F., Review of Medical Physiology, 23rd Edition, McGraw-Hill, 2009, ISBN9780071605670 Guyton, A.C., Human Physiolo...

MEMBRANES AND RECEPTORS SESSION 3 THE RESTING CELL MEMBRANE LECTURE 3.2 CHANGING MEMBRANE POTENTIALS Lecturer Dr. Safa Amir 1 References Ganong, W.F., Review of Medical Physiology, 23rd Edition, McGraw-Hill, 2009, ISBN9780071605670 Guyton, A.C., Human Physiology and Mechanisms of Disease, 6th Edition, W.B. Saunders, 1997, ISBN 0721632998 2 Changing Membrane Potentials Changes in membrane potential underlie many forms of signaling between and within cells. Examples: 1. Action potentials in nerve and muscle cells 2. Triggering and control of muscle contraction 3.Control of secretion of hormones and neurotransmitters 4.Transduction of sensory information into electrical activity by receptors 5. Postsynaptic actions of fast synaptic transmitters 3 Two widely-used terms Depolarization: A decrease in the size of the membrane potential from its normal value. Cell interior becomes less negative e.g.: a change from – 70 mV to – 50 mV Hyperpolarization An increase in the size of the membrane potential from its normal value. Cell interior becomes more negative e.g.: a change from – 70 mV to – 90 mV 4  If it becomes less negative, it is called depolarization (happens when sodium is entering the cell). If it becomes more negative than minus 70, it is hyperpolarization. (happens when K leaves the cell) In either case, when you go back towards minus 70, it is repolarization. Threshold is the point at which the first voltage-regulated sodium channel opens. Question To depolarize a cell, what kind of charge must be put into the cell, positive or negative? Positive Depolarization Stage. At this time, the membrane suddenly becomes very permeable to sodium ions, allowing tremendous numbers of positively charged sodium ions to diffuse to the interior of the axon. The normal “polarized” state of –90 millivolts is immediately neutralized by the inflowing positively charged sodium ions, with the potential rising rapidly in the positive direction. This is called depolarization. 6 Repolarization Stage. Within a few 10,000ths of a second after the membrane becomes highly permeable to sodium ions, the sodium channels begin to close and the potassium channels open more than normal. Then, rapid diffusion of potassium ions to the exterior re-establishes the normal negative resting membrane potential. This is called repolarization of the membrane. 7  Voltage-Gated Sodium Channels 8  Voltage-Gated Potassium Channel 9  Voltage Voltage gated k open gated Na open Ligand gated Na/k ATPase 10 Changing membrane ion permeability Membrane potentials arise as a result of selective ionic permeability Changing the selectivity between ions will change membrane potential Increasing membrane permeability to a particular ion moves the membrane potential towards the Equilibrium Potential for that ion K+: EK = - 95 mV Ca2+: ECa = + 122 mV Na+: ENa = + 70 mV Cl-: ECl = - 96 mV Opening K+ or Cl- channels will cause hyperpolarization Opening Na+ or Ca2+ channels will cause depolarization Thus changes in membrane potential are caused by changes in the activity of ion channels 11  Some channels are themselves less selective: Example: At the neuromuscular junction, motor neurone terminals release acetylcholine, ACh. ACh binds to receptors on the muscle membrane – Nicotinic acetylcholine receptors Nicotinic Acetylcholine Receptors 1. Have an intrinsic ion channel 2. Opened by binding of acetycholine 3. Channel lets Na+ and K+ through, but not anions 4. Moves the membrane potential towards 0 mV - intermediate between ENa and EK 12  Controlling channel activity  Channels can open and close: they are Gated  Types of Gating  1.Ligand Gating The channel opens or closes in response to binding of a chemical ligand  e.g. Channels at synapses that respond to extracellular transmitters  Ach bind to receptor cause influx ions (Na) to start muscle depolarization Channels that respond to intracellular messengers (e.g. Cyclic AMP) 13  2. Voltage Gating  Channel opens or closes in response to changes in membrane e.g. Channels involved in action potentials 3. Mechanical Gating Channel opens or closes in response to membrane deformation e.g. Channels in mechanoreceptors: carotid sinus stretch receptors, hair cells 14 Synaptic Transmission A synapse is a gap that is present between two neurones. Action potentials are propagated across the synapse by synaptic transmission (also known as neurotransmission). A neurone that sends the signal is known as the presynaptic neurone, whereas the postsynaptic neurone receives the signal. Neurotransmission starts with the release of a readily available neurotransmitter from the presynaptic neurone, followed by its diffusion and binding to the postsynaptic receptors. Then the postsynaptic cell responds appropriately, whereas neurotransmitter is removed or deactivated to allow the entire cycle to occur again. 15 16 Synaptic connections occur between: nerve cell – nerve cell nerve cell – muscle cell nerve cell – gland cell At the synapse a chemical transmitter released from the presynaptic cell binds to receptors on the postsynaptic membrane There are Fast and Slow synaptic transmission 17  Fast synaptic transmission In fast synaptic transmission, the receptor protein is also an ion channel Transmitter binding causes the channel to open 18  1- Excitatory synapses Excitatory transmitters open ligand-gated channels that cause membrane depolarization, Can be permeable to Na+ and Ca2+. The resulting change is called an Excitatory post-synaptic potential (EPSP) Excitatory transmitter or nerve stimulation. Transmitters include: Glutamate & Acetylcholine 2- Inhibitory synapses Inhibitory transmitters open ligand-gated channels that cause hyperpolarization Permeable to K+ or Cl- (Inhibitory post- synaptic potential) (IPSP) Transmitters :γ-aminobutyric acid (GABA) &Glycine 19 Postsyna@ic Potentials can be: Ex”citatorg Inhibitory post«ynapk postsyna”ptic poten.tIaIs jaotentials {ERP) (IPSéÈ = = w w + _ 20 21  Slow synaptic transmission The receptor and channel are separate proteins. Two basic patterns: 1..Direct G-protein gating 2 Gating via an intracellular messenger Receptor G-protein Channel (G- protein connected with channel) 22  Gpnńcii sub units ‹ r 23 Two other factors that can influence membrane potential 1. Changes in ion concentration Can alter membrane excitability, e.g. in heart Most important is extracellular K+ concentration (~4.5 mM normally), Sometimes altered in clinical situations (e.g in hyperkalemia). 2.Electrogenic pumps Na/K- ATPase 3 Na+ Out & 2 K+ In One +ve charge is moved out for each cycle In some cells, this contributes a few mV directly to the membrane potential, making it more negative. Some drugs inhibit the Na/K- ATPase pump, like cardiac glycosides (e.g.digoxin and ouabain. Indirectly, active transport of ions is responsible for the entire membrane potential, because it sets up and maintains the ionic gradients 24 25