PSL300 Membrane Lecture - University of Toronto PDF

PSL300 PSL300 - Lecture 03 Impulse Conduction – Excitable Cells – Cable Properties – Myelination – Conduction Velocity Axon Terminal – Vesicle Release – Synapses Impulse Conduction When a patch of excitable membrane generates an action potential, this causes...

PSL300 PSL300 - Lecture 03 Impulse Conduction – Excitable Cells – Cable Properties – Myelination – Conduction Velocity Axon Terminal – Vesicle Release – Synapses Impulse Conduction When a patch of excitable membrane generates an action potential, this causes an influx of Na+ and reverses the potential difference across the membrane. The local reversal in potential temporarily goes from “-” on the inside to “+” on the inside. This local reversal in potential serves as the source of depolarizing current for adjacent membrane Na+ channels opened in adjacent membrane Therefore, once started, an AP will propagate from its origin across the rest of the cell Impulse Conduction When a patch of excitable membrane generates an action potential, this causes an influx of Na+ and reverses the potential difference across the membrane. The local reversal in potential temporarily goes from “-” on the inside to “+” on the inside. This local reversal in potential serves as the source of depolarizing current for adjacent membrane Na+ channels opened in adjacent membrane Therefore, once started, an AP will propagate from its origin across the rest of the cell Excitable Cells Most cells are not ‘excitable’, (i.e. they do not generate APs) for the simple reason that they lack voltage- gated Na+ channels These cells will however conduct passive currents, but will not generate APs Most cells are not interested in carrying a signal any distance, they don not have an ‘axon’ An axon is a long extension of the cell body (like a wire) that carry AP away to some other location Therefore, only neurons with long ‘axons’ and muscle cells generate propagating action potentials Excitable Cells Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron AP Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell with its Dendrites body postsynaptic target cell Input Integration Output signal signal Excitable Cells Parts of a Neuron Nucleus Axon Axon (initial Myelin sheath Postsynaptic hillock segment) neuron Synapse: The region where an Presynaptic Synaptic Postsynaptic axon terminal axon terminal cleft dendrite communicates Cell with its Dendrites body postsynaptic target cell Input Integration Output signal signal Excitable Cells In biological tissue if we put a voltage across membrane on one location (i.e. step change in voltage) and measure the voltage across the membrane some distance away > It doesn’t look anything like what we started with Biological tissue Copper wire Excitable Cells In biological tissue if we put a voltage across membrane on one location (i.e. step change in voltage) and measure the voltage across the membrane some distance away > It doesn’t look anything like what we started with Biological tissue Copper wire Excitable Cells Membrane property shape the form of the signal We are losing signal as the current travel along the membrane How can we prevent this loss, how can we move this signal without signal loss? Cable Properties To describe this we’ll use the “length constant”   measures how quickly a potential difference disappears (decays to zero) as a function of distance Thus, the conduction velocity of an AP along an axon depends on the membrane length constant,  Cable Properties What are the mechanisms involved in the nervous system to improve ? –  is increased by increasing diameter (The larger the diameter > less internal resistance > less voltage is lost across that resistance as the currents travel down the membrane) –  is increased by increasing membrane resistance (The higher the membrane resistance > less current is leaked out > current is forced down the membrane) Cable Properties What are the mechanisms involved in the nervous system to improve ? –  is increased by increasing diameter (The larger the diameter > less internal resistance > less voltage is lost across that resistance as the currents travel down the membrane) –  is increased by increasing membrane resistance (The higher the membrane resistance > less current is leaked out > current is forced down the membrane) Cable Properties What are the mechanisms involved in the nervous system to improve ? –  is increased by increasing diameter (The larger the diameter > less internal resistance > less voltage is lost across that resistance as the currents travel down the membrane) –  is increased by increasing membrane resistance (The higher the membrane resistance > less current is leaked out > current is forced down the membrane) Length Constant The length constant is defined with internal resistance, extracellular fluid resistance and membrane resistance Since the extracellular fluid resistance is not adjustable and is relatively low, it drops from the equation and we’re left with internal resistance and membrane resistance Length Constant  is defined as the distance you can travel, to the point where the voltage drops to about 37% of its original value Ideally, you want to increase  as much as possible so that the depolarizing current will spread a great distance Length Constant  is defined as the distance you can travel, to the point where the voltage drops to about 37% of its original value Ideally, you want to increase  as much as possible so that the depolarizing current will spread a great distance Length Constant  is defined as the distance you can travel, to the point where the voltage drops to about 37% of its original value Ideally, you want to increase  as much as possible so that the depolarizing current will spread a great distance Myelination Increasing membrane resistance (i.e. myelination) is the most efficient means of increasing conduction velocity ‘Glial’ cells are cells that assist the nervous system, they are required for nutrition and increased membrane resistance Specialized ‘glial’ cells (Schwann cells of the PNS or oligodendrocytes within the CNS) wrap around successive sections of an axon > myelin sheath Myelination 50-100 layers wrapping around the axon > this greatly increases the membrane resistance > reduces the leakage of current out of the membrane Myelination 50-100 layers wrapping around the axon > this greatly increases the membrane resistance > reduces the leakage of current out of the membrane Myelination Schwann cell wraps around a single portion of the one axon (cytoplasm is all squeezed-out) Oligodendrocyte has a number of processes that streaks out like an octopus and wraps a whole bunch of axons individually Myelination There are small gaps left between adjacent portions of the myelin sheath (a glial cell will wrap one section and next glial cell will wrap another section) This small gap left between adjacent glial cells > the ‘Node of Ranvier’ MS Myelination There are small gaps left between adjacent portions of the myelin sheath (a glial cell will wrap one section and next glial cell will wrap another section) This small gap left between adjacent glial cells > the ‘Node of Ranvier’ MS Saltatory Conduction In myelinated axons, only the membrane exposed at the nodes is excitable Because the APs are only generated at these nodes, it means that the AP will ‘jump’ from one place to the next and in between, you’re not generating any AP This ‘jumping’ mode of conduction is known as ‘saltatory conduction’ Saltatory Conduction Thus, if we have an AP on one node, the depolarizing current that is generated at the site is strong enough and will travel down that axon for many nodes (5-10 nodes) There is sufficient strength to bring all the following nodes to threshold potential Therefore, AP at one node will bring all the next 5-10 nodes to -55 mV to generate APs on all the next nodes simultaneously and passive spread of depolarizing current occurs between the nodes (myelinated portion) myelin prevents leakage of current across membrane between nodes Saltatory Conduction APs at one node will bring all the next 10 nodes to -55 mV to generate APs What counts is the furthest node (10th node), because it will now serve as the depolarizing force for the next 10 nodes etc… Saltatory Conduction This type of conduction has a big safety factor: You could poison some of the nodes and the depolarizing current will just skip past that and move on to the next healthy patch of membrane (i.e. you have to destroy a fair length of the membrane to stop AP in its track) XX Unmyelinated Axons The unmyelinated axons do not have this extensive wrapping around the outside > you get lots of current leakage and slows down the conductance velocity Slow conduction velocity (small axon diameter and low membrane resistance) Both Na+ and K+ voltage-gated channels are intermixed Majority of axons are unmyelinated Unmyelinated Axons Unmyelinated axons do have some insulation: the schwann cell and oligodendrocyte engulf the axon (5-30 axons) without winding > “Remak Bundle” Remak Bundle Axon terminal AP will be conducted along the membrane right to the end of the cell > at the end of the cell, AP is still generating depolarizing currents So why not just go backwards to where it came from? AP cannot turn around and re- propagate in direction it came from because of refractory period, the volt-gated Na+ channels are inactivated So at the end of the axon, the AP dies-out…it can only go one way Axon terminal AP will be conducted along the membrane right to the end of the cell > at the end of the cell, AP is still generating depolarizing currents So why not just go backwards to where it came from? AP cannot turn around and re- propagate in direction it came from because of refractory period, the volt-gated Na+ channels are inactivated So at the end of the axon, the AP dies-out…it can only go one way X Refractory period Synapses Functional association of a neuron with – Another neuron – Effector organs (muscle or gland) Types – Electrical – Chemical Synapses Functional association of a neuron with – Another neuron – Effector organs (muscle or gland) Types – Electrical – Chemical Electrical Synapse At electrotonic synapses (gap junctions), adjacent membranes are about 35Å apart Gap junction bridged by connexins which allow small ions (and depolarization) to cross Synapses Functional association of a neuron with – Another neuron – Effector organs (muscle or gland) Types – Electrical – Chemical Chemical Synapse The transmitter is released into the extracellular space which exists between adjacent cells The synapse is defined by the presynaptic surface (the bouton, which contains the vesicles) and the postsynaptic membrane, which is the membrane of the adjacent neuron Synaptic cleft (the space) is about 200 Å wide This space is very specialized due to the existence of postsynaptic membrane, which contain specific protein receptors which will bind that transmitter molecule after it’s released Axon terminal Axons end in ‘boutons’ filled with vesicles vesicle are tiny organelles, which contain neurotransmitters which is released into the extracellular fluid Vesicle Release The trigger for exocytosis is always Ca++ ions How do we get the Ca++ ions in? Bouton membrane contains voltage-gated Ca++ channels which open when depolarized by AP currents AP depolarizes the bouton membrane > reaches threshold for opening volt-gated Ca++ channels (-50mV) Ca++ diffuses into bouton, and triggers cascade of reactions which result in vesicle exocytosis (commonly ‘kiss & run’ type = transient OR full fusion = all transmitters are released) Vesicle Release Normally, vesicles are docked in preparation for fusion, we have a set of vesicles which are lined-up and ready to go Synapses Are Processing Stations Chemical synapses are processing stations Note that vesicle release is probabilistic – 1 AP has a 10-90% chance of releasing 1 vesicle Synapses Are Processing Stations Chemical synapses are processing stations Note that vesicle release is probabilistic – 1 AP has a 10-90% chance of releasing 1 vesicle Thank You!