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Special features of nerves:

Special features of nerves:. Generation and conduction of electric signal Special contact with orther neurons or the innervated organs. Neurotransmitters. Nerve terminal. Nerve terminal. Axonal t ransport (enzymes for synthesis). Synthesis. Store. Release. uptake.

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Special features of nerves:

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  1. Special features of nerves: • Generation and conduction of electric signal • Special contact with orther neurons or the innervated organs

  2. Neurotransmitters

  3. Nerve terminal Nerve terminal Axonal transport (enzymes for synthesis) Synthesis Store Release uptake enzymes Inactivation Postsynaptic receptors Second messenger ion channels

  4. Neuronal receptor types

  5. Cholinergic neurons • Neuromuscular juction • Autonomic preganglionic fibers • Parasympathetic postganglionic fibers- heart, glands, smooth muscle • Central nervous system

  6. Cholinergic axon terminal

  7. 66 – 70 KDa • Immunohistochemical mapping of cholinergic neurons • Cytoplasmic • Not rate–limiting

  8. [choline]plasma ~ 10 mM • „low-affinity” choline uptake • KM>10 µM - in all tissues • „high affinity” choline uptake • Na+-dependent • KM 1-5 µM • in cholinergic neurons • inhibitor: hemicholinium

  9. Uptake of acetylcholine into vesicles transport inhibitor ~ 2000 molecules of ACh plus ATP

  10. Cholinergic receptors Muscarinic Nicotinic Postganglionic parasympathetic nerve endings Neuromuscular juction Central nervous system CURARE ATROPINE Molecular mechanism: PLC activation, [Ca]; á, Activation of K+-channels Molecular mechanism: Na+, K+-channels

  11. Receptors: Nicotinic • Ionotropic • Striatal muscle • Na+K+ permeability • Resting muscle tone • Miniature end-plate potential • Membran depol. • Ca2+ from SR • D-tubocuranine • Competitive inhibitor • CNS

  12. Receptors: Nicotinic

  13. Acetylcholine receptor:nicotin

  14. Neuromuscular junction a-bungarotoxin - obtained from the venom of an Indian snake - specifically blocksmuscular nicotinic receptors.

  15. Receptor: Muscarinic • 7 transmembrane G Protein receptor • M1 – Gq – PIP2hydrolysis • Regulation of transmitter release

  16. Receptor: Muscarinic • 7 transmembrane G protein receptor • M2 • – heart • K+ channel activation • Hyperpolarisation • Bradycardia • Giadenylate cyclase inhibition

  17. Receptor: Muscarinic • 7 transmembrane G Protein receptor • M3 • – Gastro-intestinal tract, Gq - Ca2+á • Smooth muscle contraction • Secretion stimulation • Inhibitor: atropin

  18. Acetylcholine esterase • Synaptic • Specific for ACh

  19. Pseudocholinesterase • In the plasma • function unknown • Hydrolysis other esters • Short-lasting muscle relaxants Suxamethonium

  20. Acetylcholine bound to the active site of acetylcholinesterase. This is the enzyme-substrate (ES) complex. The the bond between the choline (left side) and acetate part (right side) of the molecule has been split. Choline and acetate will leave the enzyme and it will be ready to accept another acetylcholine molecule. 16 mmol / mg / min

  21. Cholinesterase inhibitors -Diagnostic test Myasthenia gravis Autoimmune disease Antibody against nicotinic receptors -Myasthenia gravis • therapy • physostigmin, neostigmin -Eye drops • Glaucoma

  22. Diisopropyl-flurophosphate (DFP) Reversible inhibitors: neostigmine, physostigmine, gallimine Irreversible inhibitors: organic phosphates, pesticides chemical warfare

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