PowerPoint presentations for Principles of Animal Physiology by Moyes (Chapter 4)

Neuron Structure and Function Figure 4.1 Neurons Vary in structure and properties Use same basic mechanisms to send signals Code incoming information into changes in electrical potentials across cell membrane polarity Neural Zones Four functional zones Reception Dendrites and the cell body (soma) Incoming signal received and converted to change in membrane potential Integration Axon hillock Strong signal is converted to an action potential (AP) Conduction Axon (some wrapped in myelin sheath) AP travels down axon Transmission Axon terminals Release of neurotransmitter Electrical Signals in Neurons Neurons have a resting membrane potential (like all cells) Neurons are excitable Can rapidly change their membrane potential by altering permeability Act as an electrical signal Gated ion channels open or close in response to a stimulus E.g. NT Membrane Potential Factors contributing to membrane potential Distribution of ions across the membrane Relative permeability of the ions Charges of the ions Goldman equation for the calculation of membrane potential (Em) Other ions (Ca++, Mg++, etc.) are ignored in this simplified form of the equation because their permeabilities are very low Signals in the Dendrites and Cell Body Membrane-bound receptors are bound by incoming signal (e.g. NT) Receptors transduce the chemical signal to an electrical signal by changing ion permeability of membrane Change in ion permeability causes change in membrane potential (graded potential) Vary in magnitude depending on strength of stimulus More neurotransmitter ? more ion channels open ? larger magnitude of graded potential Depolarization Hyperpolarize Na+ or Ca2+ channels K+ and Cl- channels Graded Potentials Travel Only Short Distances Conduction with decrement Magnitude of graded potential decreases with increasing distance from opened ion channel Electrotonic current spread Positive charge spreads through cytoplasm causing depolarization of adjacent membrane Decrement due to: Leakage of charged ions across membrane Electrical resistance of cytoplasm Electrical properties of membrane Integration of Graded Signals Graded potentials can be generated simultaneously Many receptors and types of receptors Some excitatory – (Vm toward threshold) Some inhibitory - hyperpolarizations Spatial summation Temporal summation Action Potentials Travel Long Distances Characteristics of Action Potentials: Triggered by net graded potential at axon hillock (trigger zone) Must reach threshold potential to fire Depolarizations below threshold will not initiate an action potential All-or-none Do not degrade over time or distance Travel long distances along membrane Action Potentials (AP) Occur only when membrane potential at axon hillock reaches threshold Three phases: Depolarization Repolarization Hyperpolarization Absolute refractory period Cell incapable of generating a new AP Relative refractory period More difficult to generate new AP Table 4.1 Graded Potentials vs. Action Potentials Voltage-Gated Channels Na+ channels open first (depolarization) K+ channels open more slowly (repolarization) Na+ channels close K+ channels close slowly relative refractory period caused by open K+ channels Change shape due to changes in membrane potential Positive feedback Influx of Na+ ? local depolarization ? more Na+ channels open ? increase permeability ? more depolarization vg Na+ Channels Have Two Gates Activation gate Voltage dependent Opens when membrane reaches threshold Inactivation gate Time-dependent Closes after brief time Figure 4.12 Voltage-Gated Channels and the AP Relatively small number of ions move into and out of cell Single action potential has no measurable affect on ion concentrations inside and outside cell Na+/K+ ATPase restores concentration gradients following repeated action potentials Action Potentials Travel Long Distances Unchanged Self propagating An AP triggers the next AP in adjacent areas of membrane without degradation (all APs are the same) Electrotonic current spread Charge spreads along membrane Regenerative cycle Ion entry ?electrotonic current spread ? Trigger AP Myelination Vertebrate neurons are myelinated Myelin Insulating layer of lipid-rich Schwann cells wrapped around axon Reduce “leakage” of charge across membrane Schwann cells are a type of Glial cell Cells other than neurons that support neuron function Figure 4.14 Myelination Nodes of Ranvier Areas of exposed axonal membrane between Schwann cells High concentration of voltage-gated ion channels Internodes The myelinated region Saltatory conduction APs “leap” from node to node APs occur at nodes of Ranvier, and electrotonic current spread through internodes This type of conduction is very rapid Retrieved from http://www.biologymad.com/NervousSystem/nerveimpulses.htm#propagation Unidirectional Signals Action potentials start at the axon hillock and travel towards the axon terminal “Up-stream” Na+ channels (just behind the region of depolarization) are in the absolute refractory period The absolute refractory period prevents backward (retrograde) transmission and summation of APs Relative refractory period also contributes by requiring a very strong stimulus to cause another AP Information Transfer by AP AP frequency carries information AP frequency increases with stronger stimuli Magnitude of each AP does not change Maximum frequency is limited by the absolute refractory period Mammalian nerves can conduct 500–1000 action potentials per second The Synapse Signal transmission from neuron to another cell Synapse Presynaptic cell, synaptic cleft, and postsynaptic cell Synaptic cleft Space between the presynaptic and postsynaptic cell Postsynaptic cell May be a neuron, muscle cell, or endocrine cell E.g.Neuromuscular junction Synapse between a motor neuron and a skeletal muscle cell Figure 4.16 Signal Transmission at a Chemical Synapse Intracellular Ca2+ regulates NT release Amount of Neurotransmitter Released [Ca2+]i is affected by AP frequency More open voltage-gated Ca2+ channels ? [Ca2+]i Factors that lower intracellular [Ca2+]i Binding with intracellular buffers ? [Ca2+]i Ca2+ ATPases ? [Ca2+]i High AP frequency ? Ca2+ influx is greater than removal ? ? [Ca2+]i ? many synaptic vesicles release their contents ? high [neurotransmitter] in synapse Figure 4.17 Acetylcholine Ionotropic or metabotropic effects Primary neurotransmitter at the vertebrate neuromuscular junction Transmission of Signal Strength at Synapse Response of postsynaptic cell influenced by: Amount of neurotransmitter Rate of release – rate of removal Release determined by frequency of APs Removal determined by Passive diffusion out of synapse Degradation by synaptic enzymes (e.g. AChE) Uptake by surrounding cells Number of receptors Density of receptors on postsynaptic cell (up to saturation) Diversity of Neurons All neurons have three functions: Receive and integrate incoming signals Conduct the signal along the neuron Transmit the signal to other cells Neurons differ in their ability to receive incoming signals Different receptors Neurons differ in mechanism of signal conduction and synaptic transmission But all receive signal and transduce into an electrical signal – change in membrane potential Structural Classes of Neurons Multipolar Many dendrites One axon Bipolar One dendrite (may have branches) One axon Unipolar Single process extending from cell body May split to form afferent and efferent branches Functional Classes of Neurons Afferent neurons (sensory) Conduct action potentials towards the central nervous system Efferent neurons (motor) Conduct action potentials from the central nervous system to the organs Interneurons Conduct action potentials between neurons in the central nervous system Glial Cells Five main types of glial cells in vertebrates Schwann cell Forms myelin on motor and sensory neurons of PNS Oligodendrocyte Forms myelin on neurons in CNS Astrocyte Transport nutrients, remove debris in CNS Microglia Remove debris and dead cells from CNS Ependymal cells Line fluid-filled cavities of CNS Diversity of Signal Conduction Diverse mechanisms of signal conduction Electrotonic current spread Action potentials Saltatory conduction Chemical and electrical synapses There is also additional diversity in AP physiology: Shape and speed of action potential due to properties of Na+ and K+ channels Function of channels (molecular properties) Number of channels Some lack voltage-gated K+ channels entirely! Ion Channel Isoforms Channel isoforms encoded by different genes Voltage-gated K+ channels are highly diverse 18 genes encode for 50 isoforms in mammals Voltage-gated Na+ channels are less diverse 11 isoforms in mammals Each isoform has distinct functional characteristics Channel Density Density of voltage-gated Na+ channels affects signal conduction Increased density of channels lowers threshold Increased density of channels shortens relative refractory period Presence of voltage-gated Ca2+ channels affects AP Open at the same time or instead of voltage-gated Na+ channels Ca2+ influx is slower and more sustained than Na+ influx – longer refractory period Voltage-gated Ca2+ channels play key role in function of cardiac muscle Table 4.3 Conduction Speed of Axons Two strategies to increase conduction speed: Myelination Increasing diameter of axon Let’s look at axon properties and basic biophysics Cable Properties of Axons Similar physical principals govern current flow through axons and undersea telephone cables Current (I) Amount of charge moving past a point at a given time A function of the voltage (V) drop across circuit and the resistance (R) of circuit Voltage (V) Difference in electrical potential Resistance (R) Force opposing flow of electrical current Ohm’s law: V = I ? R Cable Properties of Axons An axon behaves like an electrical circuit Ions moving through voltage-gated channels cause current across membrane Current spreads electrotonically along axon Some current leaks out of axon and flows backwards along outside of axon, completing circuit Cable Properties of Axons Each area of axon consists of an electrical circuit Three resistors: Extracellular fluid (Re), Membrane (Rm), Intracellular fluid (Ri) A capacitor (Cm) Stores electrical charge; Two conducting materials (ICF and ECF) Insulating layer (phospholipids) Now lets see how these circuit elements affect speed of AP Voltage Decreases with Distance Change in membrane potential (voltage) during AP decreases over distance due to resistance Conduction with decrement Higher resistance of intracellular and extracellular fluids causes greater decrease in voltage along axon Lower resistance of membrane causes greater decrease in voltage along axon K+ leak channels (always open) Some + charge leaks out Number of K+ leak channels will affect current loss and voltage decrease along axon I =?V/R Length Constant (?) of Axons Distance over which membrane potential will decrease to 37% (1/e) of its original value Variables affecting length constant: Resistance of cell membrane (rm) Resistance of intracellular fluid (ri) Resistance of extracellular fluid (ro) ro is usually low and constant; and is often ignored l is largest when rm is high and ri is low Axon Membrane Capacitance Capacitance Quantity of charge needed to create a potential difference between two surfaces of a capacitor Depends on three features of the capacitor: Material properties Generally the same in cells (lipid bilayer) Area of two conducting surfaces Larger area increases capacitance Thickness of insulating layer Greater thickness decreases capacitance Time Constant (? ) Time over which membrane potential to reach 63% of its final value How well does the membrane “hold” its charge? Variables affecting time constant: Resistance of cell membrane (rm) Capacitance of the cell membrane (cm) t = rmcm Low rm or cm result in low t Capacitor becomes full faster Faster depolarization Faster conduction ? , ? and the Speed of Conduction Axonal conduction is usually a combination of electrotonic current flow and ions flowing through voltage-gated channels during an AP Electrotonic current flow is faster, but flow decreases over distance ? l - potential change at one point would spread a greater distance along the axon and bring distant regions to threshold sooner. ? ? - more rapidly a depolarization affects adjacent region and will bring the adjacent region to threshold sooner. Therefore, propagation velocity is directly proportional to space constant and inversely proportional to time constant. Figure 4.24 Giant Axons Easily visible to naked eye (up to 1 mm diameter) Not present in mammals Giant Axons Have High Conduction Speed rm inversely proportional to surface area Large diameter axons have greater surface area and more leak channels; therefore low resistance ri inversely proportional to volume Large diameter axons have greater volume; therefore low resistance As axon diameter increases, rm and ri both decrease But why does it increase conduction speed? Giant Axons Have High Conduction Speed Low rm reduces the length constant and decreases conduction speed Low ri increases the length constant and increases conduction speed Do not cancel each other out: rm is inversely proportional to radius, ri is inversely proportional to radius2 Net effect of increasing axon radius is to increase speed of conduction Figure 4.25 Axon Diameter and the Length Constant Therefore, ? radius, local currents can flow farther without degrading?faster signal conduction Myelinated Neurons in Vertebrates Disadvantage of large axons Take up a lot of space which Limits number of neurons that can be packed into nervous system Large volume of cytoplasm makes them expensive to produce and maintain Myelin enables rapid signal conduction in compact space How? Myelin Increases Conduction Speed Increased membrane resistance Insulators decrease current loss through leak channels ? rm increases ? Decreased membrane capacitance Increased thickness of insulating layer ? cm decreases ? High length constant and low time constant increase conduction speed Nodes of Ranvier are needed to boost depolarization Location is critical Synaptic Transmission Transfer of electrical signal from presynaptic cell to postsynaptic cell Electrical synapse Gap junction Chemical synapse Chemical messenger crosses synaptic cleft Electrical synapse Chemical synapse Rare in complex animals Common in complex animals Common in simple animals Rare in simple animals Fast Slow Bi-directional Unidirectional Postsynaptic signal is similar to presynaptic Postsynaptic signal can be different Excitatory Excitatory or inhibitory Electrical and Chemical Synapses Figure 4.27 Structural Diversity of Chemical Synapses Neurotransmitters Synthesized in neurons Released at presynaptic cell following depolarization Bind to a postsynaptic receptor and cause an effect More than 50 known substances Categories Amino acids Neuropeptides Biogenic amines Acetylcholine Miscellaneous (gases, purines, etc.) A single neuron can produce and release more than one neurotransmitter Neurotransmitter Action Inhibitory neurotransmitters Cause hyperpolarization of membrane Inhibitory postsynaptic potential (IPSP) Make postsynaptic cell less likely to generate an AP Excitatory neurotransmitters Cause depolarization of membrane Excitatory postsynaptic potential (EPSP) Make postsynaptic cell more likely to generate an AP Figure 4.28a Neurotransmitter Receptor Function Ionotropic receptors Ligand-gated ion channels Fast E.g: nicotinic Ach receptor Metabotropic receptors Receptor changes shape Formation of second messenger Alters ion channel Relatively slow May lead to long-term changes via other cellular functions E.g. muscarinic ACh receptors Receptors for Norepinephrine Adrenergic receptors Alpha (?) Several isoforms Metabotropic Linked to ion channel function via G-protein Beta (?) Several isoforms Metabotropic Linked to ion channel function via G-protein Synaptic Plasticity Change in synaptic function in response to patterns of use Synaptic facilitation Repeated APs result in increased Ca2+ in terminal Increased neurotransmitter release Synaptic depression Repeated APs deplete neurotransmitter in terminal Decreased neurotransmitter release Post-tetanic potentiation (PTP) After train of high frequency APs there is increased neurotransmitter release Ca2+-dependent increase in available pool of NT containing vesicles Evolution of Neurons Only metazoans have neurons Other organisms have electrical signaling Algae have giant cells that can generate APs using Ca2+ activated Cl– channels Plants have APs involving Ca2+ that travel through the xylem and phloem Paramecium can change direction as a result of APs produced by Ca2+ channels Only metazoans have voltage-gated Na+ channels Key innovation in evolution of complex nervous systems