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Neuron Function 2 Neuronal Cytoskeleton The neuronal cytoskeleton is quite important Maintenance of shape Normal neuronal metabolism Nerve terminals (axonal buds) are nurtured by materials that travel from cell body to terminals by axoplasmic flow Neuronal Cytoskeleton 2 Two prominent cytoskeletal elements Microtubules Neurofilaments- specific type of intermediate filaments (10 nm diameter) Both are extensively cross-linked to one another Neuronal Cytoskeleton 3 Actin microfilaments are also present Actin is localized immediately adjacent to PM Actin is also localized at the tip of growth cones of formative neurites in development Nerve Terminals Axoplasmic flow is the means by which the distant nerve terminals synaptic knobs are bulbs are nurtured The cell body of the cell contains the biosynthetic machinery of the cell The cytoskeleton is used to mediate transit of secretory materials out to terminals and move materials back to soma or cell body Axoplasmic flow Two general types Fast 250 to 400 mm/day; typically involves preassembly of components into membrane bound organelle or vesicle Slow 50 mm/day; cytoskeletal and cytoplasmic elements (non-membrane bound) Anterograde vs Retrograde Axoplasmic flow is bidirectional Anterograde is towards synaptic knob Retrograde is back toward soma Transit is mediated by motor proteins that hydrolyze ATP and “walk” along the microtuble or microfilament Motor Proteins Kinesin - walks toward + end (away from the cell body towards synaptic knobs) Cytoplasmic dynein - walks toward - end ( towards the cell body and away from the synaptic knob) Myosin 1 is a microfilament motor that walks at the periphery where actin microfilaments are prevalent The synapse The synapse is the narrow space that separates an axon buton or synaptic bulb from the soma or dendrite of a second neuron Two basic types of synapses Electrical synapse - rare found only in a few places in the body Chemical synapse - most frequently found type Electrical synapses Gap junctions connect the presynaptic axon terminal to the postsynaptic neuron dendrite or cell body (soma) Individual protein subunits connexins Six together make a pore connexon Cells electrically connected; thus AP passes from one directly onto the next Chemical synapses A narrow gap of around 20-40 nm exists between pre and post-synaptic membrane To transfer the signal of an arriving AP the synaptic knob (axon terminal) releases small molecules called neurotransmitters into the gap The NT’s diffuse across the gap NT’s bind to receptors in the post-synaptic membrane triggering a graded response Neurotransmitters Many different types of molecules act as neurotransmitters Binding to receptor turns the receptor form off state to on Excitatory NTs- cause depolarization Inhibitory NTs - cause hyperpolarization Types of neurotransmitters Acetyl Choline - synthesized from acetyl CoA + choline Most common outside CNS -cholinergic Biogenic Amines- adrenergic CatecholaminesEpinephrine Norepinephrine Dopamine Types of neurotransmitters Indoleamines 5-OH tryptamine or serotonin Histamine Neurotransmitters 2 Amino acids Excitatory Aspartic Glutamic Inhibitory GABA (gamma aminobutryic acid) Brain Glycine spinal cord Neurotransmitters 3 Peptides Enkephalins - methionine and leucine enkephalins (met and leu enkephalins) Endorphins a and b endorphins Substance P Neurohormones There are over 50 peptides that may be neurotransmitters or neuromodulators Neuropeptides Excite, inhibit, or modify activity of other neurons in the brain Differ from other NTs in that they tend to act on groups of neurons and have a long lasting effect Gut-Brain Neuropeptides Excite, inhibit, or modify activity of other neurons in the brain Differ from other NTs in that they tend to act on groups of neurons and have a long lasting effect Neurotransmitter Receptors Acetylcholine receptor fig 2-30 p 47 Binds two molecules of acetylcholine MW of multmeric complex 300,000 Subunit makeup a2,bgd Each subunit has about 500 amino acids GABA receptor Causes hyperpolarization by allowing Clions into the cell GABA is an inhibitory PSP Synapse Cholinergic neurotransmission 1. An arriving action potential depolarizes the synaptic knob 2. Ca+2 ions enter the cytoplasm of the synaptic knob. 3. ACh release occurs through diffusion and exocytosis of neurotransmitter vesicles 4. ACh diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane. Cholinergic neurotransmission 2 5. Chemically regulated sodium channels on the post synaptic surface are activated, producing a graded depolarization. 6. ACh release ceases because calcium ions are removed from the cytoplasm of the synaptic knob. 7. The depolarization ends as ACh is broken down into acetate and choline by ACh esterase. 8. The synaptic knob reabsorbs choline from the synaptic cleft and uses it to re-synthesize ACh. Synthesis Acetyl choline Choline + acetyl CoA --> Acetylcholine + CoA Enzyme choline acetyl transferase Inactivation of acetyl choline enzyme acetylcholine esterase breaks down acetylcholine to acetic acid plus choline The acetic acid is excreted and the choline is recycled back into the presynaptic knob of the neuron Adrenergic neurotransmission 1. Arriving potential depolarizes synaptic knob 2. Ca+2 ions enter cytoplasm triggering release of catecholamines 3. Catecholamines diffuse across the synaptic cleft and bind to receptors in post-synaptic membrane 4. Complex of catecholamines + receptor protein + adenylate cyclase produce second message inside cytosol; namely cAMP Adrenergic neurotransmission 2 5. cAMP (second message) activates chemically regulated Na+ ion channels 6. Phosphodiesterase breaks down cAMP -----> AMP 7. Catecholamines decrease due to enzymatic breakdown. Example: monoamine oxidase (MAO) and Catechol-O-methyl transferase