Download Synaptic transmission disorder

MBB 1 Lecture The Synapse Myasthenia Gravis-­‐ Synaptic transmission disorder • Extreme fatigability • Fluctuating muscle weakness • Problems chewing dysphagia and talking dysarthria • Respitory weakness (respiratory distress) • Action potentials in nerves are normal • Arises from a problem with synapses on muscles o Autoimmune disorder-­‐ immune system destroys acetylcholine receptors o Treated with anticholinesterase inhibitors-­‐ these increase and prolong the effects of Ach on the postsynaptic membrane o Also treated with immunosuppressive drugs or by removal of thymus gland Structure of synapse (refer to PowerPoint) Three types of synapses 1) Acodendritic-­‐ the terminal button synapses with a dendrite of the postsynaptic neuron 2) Axosomatc-­‐ the terminal button synapses with the cell body (soma) of the postsynaptic neuron 3) Axoaxonic-­‐ the terminal button synapses with the axon of the postsynaptic neuron • Presynaptic membrane-­‐ membrane of presynaptic terminal button • Postsynaptic membrane-­‐ membrane of postsynaptic neuron Release of neurotransmitter Vesicles contain neurotransmitter molecules An action potential in the presynaptic cell triggers vesicles to move toward the cell membrane Vesicles are guided toward membrane by proteins Guilding proteins act like ropes that help to pull the vesicle and presynaptic membrane together An influx of calcium ions into the presynaptic terminal buttons induces fusion of the two membranes (vesicle and membrane) Neurotransmitter molecule are then released into the synaptic cleft Neurotransmitter molecules diffuse across the fluid filled space. When they reach the other side they attach to binding sites of the postsynaptic receptors, which are located in the membrane of the postsynaptic cell. These channels permit the flow of specific ions into and out of the postsynaptic neuron Postsynaptic potentials can be either excitatory (increased likelihood of depolarization) of inhibitory (increased likelihood of hyperpolarization) Three types of neurotransmitter 1) Sodium – excitatory 2) Potassium-­‐ inhibitory 3) Chloride-­‐ inhibitory Excitatory postsynaptic potentials (EPSPs) depolarize the postsynaptic cell membrane and increase the likelihood that action potential will be triggered in the postsynaptic neuron There may be multiple synapses releasing neurotransmitters to the neuron Inhibitory postsynaptic potentials hyperpolarize the postsynaptic cell membrane and decrease the likelihood that an action potential will be triggered. The combined effect of EPSPs and IPSPs is called neural integration (counteraction). Two mechanisms ensure that any excess neurotransmitter substances left in the synaptic cleft are mopped up. 1) Reuptake-­‐ the neurotransmitter is removed from the synaptic cleft via special transporter molecules in the terminal button. These molecules use energy to draw the neurotransmitter back into the cytoplasm of the presynaptic neuron 2) Enzymatic deactivation-­‐ an enzyme in the synaptic cleft destroys the remaining neurotransmitter molecules. Occurs for only one neurotransmitter (acetylcholine) These processes ensure that the postsynaptic receptors are only exposed to neurotransmitter for a very brief period Summary of action 1) Neurotransmitter molecules synthesized from their precursors by enzymes 2) NT molecules stored in vesicles 3) Nt molecules leak from vesicles destroyed by enzymes 4) AP cause vesicles to fuse with presynaptic cell membrane, releasing NT to the synaptic cleft 5) Released NT binds with auto receptors TBC Neurotransmitters • Amino acids § Glutamate (most common excitatory) § GABA (most common inhibitor) • Monoamines (synthesized from a single amino acid (brainstem mainly) o Catecholamine § Dopamine § Norepinephrine o Indolamines § Serotonin • Acetylcholine (operates at synapses with muscles) § Acetylcholine Effects of drugs on synaptic functions • Drugs act upon the CNS in many different ways o Agonists-­‐ increase the function of Synapses and AP § Increase number of NT molecules synthesized (L-­‐dopa on dopamine) § Increase number of NT molecule in vesicles § Destroy enzymes that attack NT Molecules Increase number of Vesicles that fuse with PCM Decrease activity of auto receptors (Black widow spider venom, release of Ach) § Bind directly with postsynaptic membrane, causing ion channels to open (nicotine stimulates Ach receptors) § Decrease the amount of NT that is reuptaken or destroyed by enzymes (Amphetamine, cocaine, methylphenidate-­‐ on dopamine) o Antagonists-­‐ decrease the function of synapses and reduce AP § Decrease the number of NT synthesis (PCPA inhibits serotonin) § Decrease number of NT molecules stored in vesicles (Reserpine prevents monoamines in vesicles) § Cause NT to leak from vesicles where they are attacked by degrading enzymes § Decrease number of vesicles that fuse with PCM (Botulinum toxin release of ACh § Increase activity of auto receptors (apomorhpine stimulates dopamine auto receptors, inhibits release of dopamine) § Block the inotropic receptor, preventing the ion channels from opening (curare blocks postsynaptic Ach receptors, paralysis) § Increasing the amount of NT that is reuptaken or destroyed by enzymes in the synapse SLIDE 21 OF LECTURE 3 PROJECTION PATHWAYS §
§