BISC 307L 1st Edition Lecture 7 Current Lecture Synaptic Transmission Continued Steps in Chemical Synaptic Transmission o 1 Synthesis synthesis of transmitter from precursor enzymatic synthesis enzymes needed are made in the cell body of the neuron because only in the cell body are there organelles responsible for protein synthesis travel along using axoplasmic transport presynaptic terminal usually local one exception is the peptide transmitters which are made in the cell body o 2 Storage in vesicles packaged into these vesicles using active transport neurotransmitters highly concentrated in the vesicles o 3 Release across synapse when action potential comes down the axon and invades the terminal o 4 Receptor interaction 1 ionotropic neurotransmitter affects ion channels and causes current flow in postsynaptic cell 2 metabotropic neurotransmitter ahs metabolic affect on postsynaptic cell regeneration of second messengers Paracrine signaling and endocrine signaling are common with chemical synapses o 5 Inactivation getting rid of the neurotransmitter 3 mechanisms Fate of neurotransmitter 1 Hydrolysis by a specific enzyme either on the postsynaptic membrane or on the presynaptic membrane or in the synaptic cleft neuromuscular junction Acetylcholine in neuromuscular junction 2 Diffusing out of the synaptic cleft taken up by glial cells or just diffuse away 3 Reuptake by secondary active transporters back into the synaptic terminal Neurotransmitter Release o Example of release step o The red part is the action potential o In some synapses there are Na K voltage gated channels invading the entire terminal in big neurons o In small neurons doesn t really matter how far the depolarization extendsdon t need an action potential If the length constant of the axon is long relative to the distance between presynaptic membrane and axon you don t need an action potential o Blue blocks apparatus for the membranes to dock and release contents by exocytosis o Green ovals voltage gated Ca2 channels Ca2 enters cell down strong electrical gradient and the rise in internal Ca2 levels are toxic so causes exocytosis very locally 120 different proteins on the surface of vesicles Release by exocytosis Fusion of the vesicle membrane with the presynaptic membrane and the neurotransmitter comes out fast Classical understanding vesicle collapse and retrieval Remains its own membrane once it releases the neurotransmitter Pushes the previously fused membrane off to the side Known to occur at most synapses Modern understanding kiss and run Vesicle gets very close to the membrane does not collapse into it but fuses into it and keeps integritythere is a pore Steps in Chemical Synaptic Transmission repeated Response of postsynaptic cells o o ON the Right side Neurotransmitter binding to the metabotropic receptor activating a second messenger pathway o Two types of ionotropic mechanism from above Left Channel These channels were originally closed but binding of neurotransmitter causes them to open 1 On left pathway when the neurotransmitter binds to the Na gated ion channel receptor Ion channel is open o Na channel open Na influx which will depolarize cell EPSP closer to threshold o Increases the probability that the postsynaptic cell will have an action potential 2 On right pathway Ion channel open K channel or Clchannel EITHER CASE RESULTS IN INHIBITION if K channel opened the K equilibrium potential is going to be more negative than the membrane potential so there will be a positive driving current net outward current off K hyperpolarizing the cell Because K has a positive charge If Cl Channel Cl Equilibrium potential is also more negative than membrane potential so positive current so if opened there will also be an outward Cl current from Cl moving in because Cl has a negative charge Less likely that cell will produce action potential Middle Channel Normally open channel that a neurotransmitter binding closes o Left Side pathway Less Na ion in Reduces leakage of Na causing repolarization Rods and cones in retina o Right side K Ion channel closing that was open so there was outward K current but now that its closed there is no leakage of K out of cell causing depolarization Myasthenia Gravis o Disease that affects the neuromuscular junction Muscle weakness Autoimmune disease The body inappropriately makes antibodies directed against acetylcholine receptors at the neuromuscular junction ionotrophic channel Antibodies bind to this receptor and the acetylcholine receptors are damaged and lost deficit in acetylcholine receptors causing muscle weakness The eyelid muscles and the eyeballs are very common Ptosis left eyelid droops Diplopia two eyes won t look in the same direction Diagnose this by stimulating the nerve repetitively in normal cases you will see a large depolarization and action potential that is highly reliable The delay between when the nerve was stimulated and when the action potential occurs is pretty constant For MG patients a lot of the EPSPs are not strong enough to produce action potential not constant not reliable Single fiber electromyography Easier to do Put needle electrodes into a superficial muscles that are affected Find a place where you can record action potential in between two fibers of the same unit If patient is normal Left it will activate an action potential in both fibers in a pair Get about the same action potential in both fiber 1 and 2 Patient with MG Right the second action potential does not occur reliable in fiber 2 Recording current flowing through ht he extracellular fluid next to a muscle fiber Above is the affect of a drug on this disease Synaptic Transmission Part 2 Synaptic Transmission in the CNS o 10 2 10 3 inputs per cell o each input weak o integration determines overall effect o excitation and inhibition o different transmitters o different receptors for each transmitter o ionic and metabolic effects