Lec 3+4 RMP & AP & ST PDF

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0  0                    Resting Membrane Potential    VERSION 3 Othman Al-Shboul     Faris Katbi     Mo-Rami        1 No work Plasma membrane Potential?? What is potential? Charged particle has the ability to do work. So, charges are able to make each other or other objects move. (kinetic and potential energy)  Membrane Potential: Separation of charges across the membrane  Potential is measured in units of volts (or millivolt (mV)).  Here we have charged particles separated by membrane:  + & - charges are equally balanced on each side of the membrane  NO Potential.  + & - charges are unequally separated across the membrane  HAS Potential.  ↑ number of charges separated  ↑ potential  Magnitude of the potential depends on the degree of separation of the opposite charges.  If you increase charged substances, you will increase the potential.  Diffusion: the movement of atoms or molecules from an area of higher concentration to an area of lower concentration. Open channels Diffusion uncharged particles We have Concentration Gradient NO Concentration Gradient  Concentration Gradient: exists when there is unequal concentration across a membrane. Open channels Only to K+ We have Concentration Gradient  NO Concentration Gradient charged particles  We have Electrical Gradient  Electrical Gradient: exists when there is unequal distribution of charges across a membrane.  Electrochemical Gradient: Exists when there is a concentration and an electrical gradient (difference)  Equilibrium Potential (Eion): when Concentration Gradient = Electrical Gradient but in opposite direction and no further NET movement of ion, BUT still we have movement.  The potential measured at this equilibrium = ion equilibrium potential (E-ion).  2 If you look here, we don’t have a channels Do we have concentration gradient? YES Can we get diffusion? NO Do we have AP? NO, we don’t have Unequal distribution of ions If you look here, we don’t have selective permeability Do we have concentration gradient? YES Can we get diffusion? YES Do we have AP? NO, after diffusion we have Electro-neutrality We don’t have excess positivity, we don’t have excess negativity, SO We don’t have action potential  Membrane Potential, in our Body:  We have Electrical charges in the body are carried by ions.  Anions (negatively charged): large intracellular proteins (A-).  Cations (positively charged): Na+, K+, Ca++.  Resting Membrane Potential (RMP)  When the cell is not sending electrical signals (i.e., at rest)  All body cells have a resting membrane potential.  Excitable Cells: ONLY Excitable Cells are able to change RMP (can be stimulated to create an electric current)  Example: 1) Nerve cells (neurons) 2) Muscle cells  How to generate membrane potential in our body cells? 2 factors 1) Unequal distribution of ions. 2) Selective permeability of plasma membrane. At rest, K+ >>> Na+ Large intracellular proteins (A-) don’t leave ICF  Inside of the plasma membrane is always negative with respect to outside at rest.  Great permeability to K+, Low permeability to Na+.  Let’s talk about plasma membrane from neuron:  The sign always designates the polarity of the excess charge on the inside of the membrane  So, + 70 mV is NOT greater than - 70 mV.  +&- Just indicate the charge distribution inside the cell  The sign indicates polarity inside the membrane  Polarity: different in charge distribution  Role of Plasma Membrane: 1) To maintain the Separation of ions and charges (Lipid bilayer does not allow polar/charged molecules to cross) 2) Selective passage (Due to presence of membrane proteins, ion channels and transporters selective for specific ions)  3  Role of Membrane Proteins: 1) Sodium – Potassium Pump: (requires energy “ATP”) Pumps 3 Na+ out for every 2 K+ in Participates in 20% of the membrane potential Unequal transport, Active transport. 2) Diffusion of Na+ & K + through their Leak channels Ions diffuse according to their electrochemical gradient Participates in 80% of the membrane potential ‫هسا يا جماعة الخير بدنا نوخذ حاالت افتراضيه للخلية على شان نقدر نفهم بالتفصيل كيف ايوني الصوديوم و البوتاسيوم بساهمو في انه يكون غشاء الخيلة من الداخل سالب‬  Equilibrium Potential of K+ (E-K+) ‫يعني بدنا نفترض انه عندي خلية عصبية فيها بوتاسيوم فقطط‬  We have a K+ leak channel.  We have higher conc inside the cell.  The ion will start to move from high to low according to Concentration Gradient.  Then will move according to Electrical Gradient.  when Concentration Gradient = Electrical Gradient  if we give voltmeter and Measure the potential there, the reading will be = -90mV  Equilibrium Potential of Na+ (E-Na+)  We have a Na + leak channel.  We have higher conc outside the cell.  The ion will start to move from high to low according to Concentration Gradient.  Then will move according to Electrical Gradient.  when Concentration Gradient = Electrical Gradient  if we give voltmeter and Measure the potential there, the reading will be = +60mV  Chloride ion they have higher conc outside the cell, BUT doesn’t play role in RMP.  AGAIN, this is imaginary situation we don’t have one type of ion in the cell.  In a real cell like nerve cells:  RMP=-70Mv.  At rest, all cells have a negative internal charge and unequal distribution of ions, resulting from: 1) Na+/K+ pump (3Na+ out vs. 2K+ in). 20% 2) High K+ permeability (70 times more than Na+) through K+ leak channels (high inside). 75% 3) Limited Na+ permeability through Na+ leak channels (high outside). 5%  We didn’t reach Equilibrium for ant types of ion bcz ((K+=-90)) and ((Na+=+60)) and ((RMP=-70Mv)).  SO all the times K+ and Na+ move in NET movement.  We have equation to calculate the membrane potential for single ion like Nernst equation  We have equation to calculate the membrane potential for more than one ion like goldman equation ‫ذكرهم الدكتور لكن مش مطلوبات منكم حطيتهم للشموليه‬  The movement of K+ in a leak channel play more important role in developing the membrane potential.  4  Excitable tissues They are responding to varies stimuli by rapidly changing their resting membrane potentials and generating electrochemical impulses. There are two types of excitable tissues: A. Nerve  (to conduct messages) B. Muscle  (to contract)  Let’s talk about nerve cells (neuron) We have RMP= -70 Mv. If we have stimulation (touch, smell, seeing)  RMP will be changed. What is the type of changing? 1) Depolarization: if the MP become more positive 2) Repolarization: if the MP backward to RMP (after depolarization) 3) Hyperpolarization: if the MP becomes more negative than RMP  Mechanism of excitation: By rapid changes in permeability to ions (Na+ & K+). By affecting voltage-gated “VG” channels (Sensitive to changes in MP).  Action Potential: A wave of MP change that sweeps along the membrane.  Action potential: spreads (moves) throughout the membrane in undecreasing fashion.  Mechanism of Action Potential 1) The cell in resting state and RMP = -70 mV and all of the gated sodium and potassium channels are closed. 2) When the stimulus reach the threshold = -55 mV, VG Na+ channels open significantly  Rapid membrane depolarization by rapid Na+ influx. becomes 600 times more permeable to Na + than to K + 3) When Na+ entering the cell, the membrane potential will change from -70 to +30 (peak potential) maximum positive value. 4) Closure of Na+ VG Channels (Na+ Influx) & Opening of K+ VG channels (K+ Efflux) which is called Repolarization. 5) Hyperpolarization Voltage-gated K+ remain open after the potential reaches RMP, which reach around -90 mV. 6) Finally, the cell will back to resting state.  5  Notes  Both depolarization and repolarization occur via diffusion  Do NOT require active transport  In depolarization we have Positive feedback effect   If the stimulus didn’t reach the threshold, the action potential won’t generate.  Before reaching the threshold, this potential change called Graded potential  At the end of repolarization phase, the membrane potential reaches -70 mV.  But Na+ are inside and K + are outside.  To restore normal situation Na+ / K + pump starts to work pushing Na+ outside and to carry K + inside the cell, returning to the resting state in which Na+ out and K + in.  During AP we don’t need energy, after AP we need energy.  Characteristics of Action Potential: 1) The action potential is an all-or none response.  It means that if the membrane is depolarized to its threshold level, an action potential will be produced.  And if the membrane is not depolarized to its threshold level, no action potential is produced.  This means that it either responds or it does not. 2) Stimulus Intensity is Coded  If the stimulus strength is increased, there will be no change in the magnitude of AP  Stronger stimulus  increase number of Aps,  frequency ((NOT stronger AP/ larger AP)).  Also strong stimulus causes more cells to reach its threshold.  The magnitude of the action potential is fixed 3) Refractory Period  The period of time during which a cell is incapable of repeating an action potential.  The amount of time it takes for an excitable membrane to be ready for a second stimulus once it returns to its resting state following an excitation.  RP is divided into two phases: a) Absolute RP  a second action potential cannot be produced  due to inactivated Na+ channels  no matter how strong is the stimulus.  The membrane will not respond to a second stimulus at all.  It starts from the beginning of the threshold period  It ends when the membrane returns to its resting potential. b) Relative RP  a second action potential can be produced.  Due to continued outward diffusion of K+  But a stronger stimulus is required.  The refractory period prevents backwards current flow.  6  Pharmacological Blockers of Na+ & K+ Channels 1) Tetrodotoxin (TTX)  isolated from puffer fish  VG Na+ channels blocker  Action potential will not occur 2) Tetraethylammonim (TEA)  K+ Channel blocker  AP can occur  but it will have an abnormally long duration  since repolarization will depend solely on Na+ channel inactivation without assistance from K+ channels Neuron  The parts of neuron: 1) Cell body: inside it (nucleus) contains DNA 2) Dendrites: (receiving inputs) they receive signal from Another neuron (signal toward the cell body). 3) Axon hillock: is the first part of the axon plus the part of the cell body where the axon exits. 4) Axon: (conduction zone) from cell body to last part in neuron (signals away from the cell body). 5) Myelin sheath … 6) Axon terminals (output zone) send signal to another neuron  Direction of signal (one way): Dendrites  Cell body  Axon  Axon terminals  Myelinated vs. Unmyelinated  Myelin is a lipid-rich (fatty) substance.  Myelin serves as an insulator/resistor electrically insulates & prevents ion leakage  Faster speed in conducting action potential  Site of AP Initiation  Axon hillock: The first portion of the axon plus the region of the cell body from which the axon leaves.  Also called neuron’s trigger zone.  Why here? Abundance of voltage-gated Na+ channels  It has the lowest threshold for the action potential  7  Conduction (Propagation) of AP  Methods of Conduction: 1) Contiguous Conduction  Local Current Flow, in unmyelinated nerve fiber.  Once an action potential is initiated in one part of a nerve cell membrane, a self-perpetuating cycle is initiated  so that the action potential is propagated along the rest of the fiber automatically  The original action potential does NOT travel along the membrane  It triggers an identical new action potential in the adjacent area of the membrane  “Backward” current flow does not re-excite previously active area because this area is in its refractory period.  “Forward” current flow excites new inactive area. (one way)  This process being repeated along the axon’s length  Spread of AP along every patch of the membrane down the axon.  A refractory period ensures one-way travel of an AP 2) Saltatory Conduction:  in myelinated nerve fibers  Gaps in myelin are called Nodes of Ranvier.  Ions can't flow across myelinated membrane, thus no APs occur under myelin, APs occur only at nodes.  VG Na+ channels are present only at nodes  After generation of AP at 1st node, local depolarization moves to the next node (under myelin) where it depolarizes next node to threshold and triggers another AP  APs jump from node to node.  Multiple Sclerosis  Auto-immune disease.  Immune-mediated inflammatory demyelinating disease of the CNS.  It will affect the conduction of AP  MANY PROPLEMS The End  8 Synaptic Transmission  Remember: we talk in the last lectures about RMP and the changes in RMP produce (fire, impulse, signal) which mean Action Potential, and we focus in AP in neuron, and we learned AP start in specific area in neuron (triggered zone) which called Axon Hillock. And we learned how the AP conduct in the neuron (Contiguous or Saltatory) depend in the type of neuron.  In this lecture we will talk about the transmission of AP from one neuron to another neuron via synapse.  A synapse is a junction between two neurons (axon terminal with dendrite). Types of synapses: 1) Electrical: rare in nervous system direct contact via gap junction bidirectional conduction found in smooth & cardiac muscles, brain, & glial cells not important in this lecture. 2) Chemical: transmission via neurotransmitters (NTs) we don’t have direct contact. Synaptic cleft (space) separates presynaptic cell from postsynaptic cell The axon terminal of a presynaptic neuron can discharge a neurotransmitter. The neurotransmitter can diffuse across the synapse and excite a postsynaptic neuron. Unidirectional conduction (unlike electrical). We have 1000 of synapses between 2 neurons.  Neurotransmitters (NTs) NTs are in synaptic vesicles. (not stored free in cytosol) Amount of NTs released depends upon frequency of APs reaching presynaptic membrane We have many type of NTs:  Acetylcholine  Aspartate  Histamine  Serotonin  Dopamine  Glycine  Epinephrine  Glutamate (excitatory)  Norepinephrine  Gamma-aminobutyric acid (GABA) (inhibitory) Some NTs act as excitatory (cuz depolarization) and some inhibitory (cuz hyperpolarization) When action of the neurotransmitter on its receptors is completed, it must be removed from the synaptic cleft  Inactivation, Uptake, Washing out.  9  Steps of Neurotransmitter Release: 1) When AP reaches the axon terminal (synaptic knob). 2) It opens Ca+2 channels which allow Ca+2 to enter the knob (through voltage-gated channels). 3) Ca+2 ions cause release of the neurotransmitter from the presynaptic knob into synaptic cleft by EXOCYTOSIS process.  Without Ca+2 we can’t release of the neurotransmitter. 4) The neurotransmitter reacts with its receptors on sub-synaptic membrane (postsynaptic neuron) causing changes in the permeability of this membrane for ions.  The action of the neurotransmitter on ions channels in sub-synaptic membrane is example chemical-gated channels. 5) The changes in the postsynaptic neuron by neurotransmitter could be excitatory or inhibitory.  Triggering signal (postsynaptic potential)  The time needed for AP to cause the release of the neurotransmitter into synaptic cleft and produce its effect on postsynaptic neuron is called synaptic delay (It is about 0.5-1 m-sec).  We said the axon hillock is the part which can be generate the AP but the synapse is far away from hillock.  The first regions receive AP are dendrites and cell body’s.  Can the dendrites generate AP? NOO, we can generate only Postsynaptic potential (NOT AP).  Okay, how we can generate AP in hillock? Postsynaptic potential in dendrites & cell body  If reaching threshold  Action potential axon hillock.  10  There are two types of synapses: 1) Excitatory synapse:  This produces an excitatory postsynaptic potential (EPSP).  EPSP and tends to depolarize the neuron.  This type of synapse is always excitatory.  In these synapses, the neurotransmitter causes opening of Na+ channels in subsynaptic membrane.  Ions enter the postsynaptic neuron, decreasing the negativity inside it (depolarization) bringing these neurons closer to its threshold.  Example for neurotransmitter secreted at excitatory synapse in the brain is Glutamate. 2) Inhibitory synapse:  It produces an Inhibitory postsynaptic potential (IPSP).  It tends to hyperpolarize the neuron.  This type of synapse is always inhibitory.  The neurotransmitter causes opening of Cl- or K+ channels.  Movement of Cl- into the cell or K+ outside the cell will increase the negativity inside postsynaptic neuron (hyperpolarization).  This moves the postsynaptic neuron away from its threshold.  Example for neurotransmitter secreted at inhibitory synapse in the brain is GABA. Now we generate postsynaptic potential but one postsynaptic potential doesn’t enough to reach threshold. It is GRADED: changes in membrane potential vary in size postsynaptic potential graded (not all or none) but AP not graded (all or none) Okayyy, now we have many postsynaptic potentials and we need to summate them.  Summation of postsynaptic potentials:  The effect of one EPSP can never increase the neuronal potential to reach its threshold.  In order to causes excitation (action potential), we need several EPSPs to be added together to cause action potential.  Summation can be done by: 1) Temporal summation: Many EPSPs from one synapse occurring very close in time (rapid succession). 2) Spatial summation: Many EPSPS from many synapses occurring at the same time (simultaneously).  If an IPSP occurs with an EPSP at the same time, their effects can either completely or partially cancel each other. The End