Ch 8: Neurons: Cellular and Network Properties Objectives: Describe the Cells of the NS Explain the creation and propagation of an electrical signal in a nerve cell Outline the chemical communication and signal transduction at the synapse Organization of NS Afferent division New 3rd division: Enteric NS Compare to Fig 8-1 Efferent division Cells of NS • Nerve cell = Neuron • Support cells = Fig 8-2 Neuron: functional unit of nervous system – excitable can generate & carry electrical signals • Neuron classification either structural or functional (?) Fig 8-3 Axonal Transport What is it? Why is it necessary? Slow axonal transport (.2 - 2.5 mm/day) Carries enzymes etc. that are not quickly consumed – Utilizes axoplasmic flow Fast axonal transport (up to 400 mm/day) Utilizes kinesins, dyneins and microtubules Actively walks vesicles up or down axon Fig 8-4 Neuroglia cells In CNS: 1. 2. 3. 4. Oligodendrocytes Astrocytes Microglia (modified macrophages) (Ependymal cells) In PNS: 5. Schwann cells 6. Satellite cells See Fig 8-5 Electrical Signals in Neurons Changes in membrane potential are the basis for electrical signaling Only nerve and muscle cells are excitable (= able to propagate electrical signals) Review “resting membrane potential” (Ch 5) Factors influencing membrane potential 1. 2. Membrane Potential Review Nernst equation describes equilibrium potential for single ions Goldman-Hodgkin-Katz (GHK) equation considers contribution of all permeable ions to membrane potential Resting membrane potential of cell is based on combined contributions of conc. gradients and membrane permeability for Na+, K+ (and Cl-) Depolarization / Hyperpolarization • Due to net movement of ions across cell membrane • Very few ions need to move for big change in membrane potential membrane potential changes but ion conc. stays the “same” • Gated ion channels control membrane permeability – Mechanically gated channels – Chemically gated channels – Voltage-gated channels Two Types of Electrical Signals Graded potentials variable strength travel over short distances only Action potentials constant strength travel rapidly over longer distances initiated by strong graded potential Start using 10 SYSTEM SUITE Four Basic Components of Signal Movement Through Neuron 1. Input signal (Graded Potential) 2. Integration of input signal at trigger zone 3. Conduction signal to distal part of neuron (= Action Potential) 4. Output signal (usually neurotransmitter) Input Signal: Graded Potentials Location? - How created? Strength (= amplitude) reflects strength of triggering event Travel over short distances to trigger zone Diminish in strength as they travel May be depolarizing (excitatory) or hyperpolarizing (inhibitory) Figs 8-7/8 Graded Potentials Diminished strength due to 1. Current leak 2. Cytoplasmic resistance Fig 8-7 Subthreshold potential vs. Suprathreshold potential Fig 8-8 Graded potential starts here Trigger zone AP Conduction Signals: Action Potentials (AP) Location ? Travel over long distances Do not loose strength as travel they Compare to Fig 8-9 Are all identical (all-or-none principle): 100mV amplitude Represent movement of Na+ and K+ across membrane Ion Movement across Cell Membrane During AP Sudden increase in Na+ permeability Na+ enters cell down electrochemical gradient (+ feedback loop for ~ .5 msec) Influx causes depolarization of membrane potential = electrical signal What stops + feedback loop? Na+ Channels in Axon Have 2 Gates Activation gate and Inactivation gate Na+ entry based on pos. feedback loop needs intervention to stop Inactivation gates close in delayed response to depolarization Fig 8-10 stops escalating pos. feedback loop AP-Graph has 3 phases – Rising (Na+ permeability ) – Falling (K + permeability ) – “Undershoot” or ________ Absolute & Relative Refractory Periods No movement of Na+ possible Na+ channels reset to resting state; K+ channels still open > normal stimulus necessary Purpose of Refractory Periods 1. Limit signal transmission rate (no summation!) 2. Assure one way transmission! Forward current excites, backward current does NOT re-excite ! Fig 8-15 Other Characteristics of APs • Stimulus intensity encoded by AP frequency • One graded potential triggers burst of APs • Amount of NT released at axon terminal is to AP frequency • One AP does not change ion conc. gradients Conduction speed depends on . . . . Axon diameter Size constraints on axons become problem with increasing organismal complexity Fig 8-17 Membrane resistance High resistance of myelin prevents current flow between axon and ECF saltatory conduction from node to node Fig 8-18 Alteration of Electrical Activity • Various chemical factors responsible, e.g.: Procaine blocks Na+ channels • Altered potassium levels will change resting membrane potential – Hyperkalemia ? – Hypokalemia ? – Gatorade and other sports drinks Output Signal: Cell to Cell Communication at Synapses Synapse = point where neuron meets target cell (e.g. ?) 2 types chemical electrical 3 components of chemical synapse presynaptic cell synaptic cleft postsynaptic cell Chemical Synapses = Majority of synapses Neurotransmitters carry info from cell to cell Axon terminals have mitochondria & synaptic vesicles containing neurotransmitter Fig 8-20 Events at the Synapse AP reaches axon terminal Voltage-gated Ca2+ channels open Ca2+ entry Ca2+ is signal for neurotransmitter release Exocytosis of neurotransmitter containing Fig 8-21 vesicles Fig 8-21 3 Classes of Neurotransmitters (of 7) 1. Acetyl Choline – Synthesized in axon terminal from acetyl CoA and choline – Quickly degraded by ACh-esterase – Cholinergic neurons – Different receptor types: – nicotinc – muscarinic Fig 8-22 2. Amines – Serotonin (tryptophane) and Histamine (histidine) – Dopamine and Norepinephrine (tyrosine) – Widely used in brain, role in emotional behavior (NE used in ANS) – (Nor)adrenergic neurons – Different receptor types ( and β) 3. Gases – NO (nitric oxide) and CO Postsynaptic Responses Can lead to either EPSP or IPSP Any one synapse can only be either excitatory or inhibitory Fast synaptic potentials Opening of chemically gated ion channel Rapid & of short duration Slow synaptic potentials Involve G-proteins and 2nd messengers Can open or close channels or change protein composition of neuron Fig 8-23 Fig 8-23 Integration of Neural Information Transfer Convergence and divergence Fig 8-26 Multiple graded potentials are integrated at axon hillock to evaluate necessity of AP Spatial Summation: stimuli from different locations are added up Temporal Summation: sequential stimuli added up Synapse: Most Vulnerable Step in Signal Propagation Many disorders of synaptic transmission, e.g.: • • • • Myastenia gravis (PNS) Parkinson’s (CNS) Schizophrenia (CNS) Depression (CNS) Mysterious paralysis