Synaptic Transmission ContinuedSteps in Chemical Synaptic Transmission1. Synthesissynthesis 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 synthesistravel along using axoplasmic transportpresynaptic terminalusually local, one exception is the peptide transmitters which are made in the cell body2. Storagein vesiclespackaged into these vesicles using active transportneurotransmitters highly concentrated in the vesicles3. Releaseacross synapsewhen action potential comes down the axon and invades the terminal4. Receptor interaction1. ionotropicneurotransmitter affects ion channels and causes current flow in postsynaptic cell2. metabotropicneurotransmitter ahs metabolic affect on postsynaptic cellregeneration of second messengersParacrine signaling and endocrine signaling are common with chemical synapses5. Inactivationgetting rid of the neurotransmitter3 mechanisms: Fate of neurotransmitter1. 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 junction2. 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 terminalNeurotransmitter ReleaseExample of release stepThe red part is the action potentialIn some synapses there are Na+/K+ voltage gated channels invading the entire terminal- in big neuronsIn small neurons- doesn’t really matter how far the depolarization extends- don’t need an action potentialIf the length constant of the axon is long relative to the distance between presynaptic membrane and axon you don’t need an action potentialBlue blocks = apparatus for the membranes to dock and release contents by exocytosisGreen ovals= voltage gated Ca2+ channelsCa2+ enters cell down strong electrical gradient and the rise in internal Ca2+ levels are toxic so causes exocytosis very locally120 different proteins on the surface of vesiclesRelease by exocytosisFusion of the vesicle membrane with the presynaptic membrane and the neurotransmitter comes out fastClassical understanding: vesicle collapse and retrievalRemains its own membrane once it releases the neurotransmitterPushes the previously fused membrane off to the sideKnown to occur at most synapsesModern understanding: kiss and runVesicle gets very close to the membrane does not collapse into it but fuses into it and keeps integrity- there is a poreSteps in Chemical Synaptic Transmission repeatedResponse of postsynaptic cellsON the Right side: Neurotransmitter binding to the metabotropic receptor activating a second messenger pathwayTwo types of ionotropic mechanism from above: Left ChannelThese channels were originally closed but binding of neurotransmitter causes them to open1. On left pathway- when the neurotransmitter binds to the Na+ gated ion channel/receptorIon channel is openNa+ channel openNa+ influx which will depolarize cellEPSP (closer to threshold)Increases the probability that the postsynaptic cell will have an action potential2. On right pathway- Ion channel open (K+ channel or Cl- channel)- EITHER CASE RESULTS IN INHIBITIONif 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 chargeIf 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 chargeLess likely that cell will produce action potentialMiddle Channel: Normally open channel that a neurotransmitter binding closesLeft Side pathwayLess Na+ ion inReduces leakage of Na+ causing repolarizationRods and cones in retinaRight sideK+ 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 depolarizationMyasthenia GravisDisease that affects the neuromuscular junctionMuscle weaknessAutoimmune diseaseThe body inappropriately makes antibodies directed against acetylcholine receptors at the neuromuscular junction- ionotrophic channelAntibodies bind to this receptor and the acetylcholine receptors are damaged and lost- deficit in acetylcholine receptors causing muscle weaknessThe eyelid muscles and the eyeballs are very commonPtosis- left eyelid droopsDiplopia- two eyes won't look in the same directionDiagnose this by stimulating the nerve repetitively- in normal cases you will see a large depolarization and action potential that is highly reliableThe delay between when the nerve was stimulated and when the action potential occurs is pretty constantFor MG patients- a lot of the EPSPs are not strong enough to produce action potential- not constant, not reliableSingle fiber electromyographyEasier to doPut needle electrodes into a superficial muscles that are affectedFind a place where you can record action potential in between two fibers of the same unitIf 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 2Patient with MG- (Right) the second action potential does not occur reliable in fiber 2Recording current flowing through ht he extracellular fluid next to a muscle fiberAbove is the affect of a drug on this diseaseSynaptic Transmission Part 2Synaptic Transmission in the CNS10^2-10^3 inputs per celleach input weakintegration determines overall effectexcitation and inhibitiondifferent transmittersdifferent receptors for each transmitterionic and metabolic effectsBISC 307L 1st Edition Lecture 7Current Lecture Synaptic Transmission Continued- Steps in Chemical Synaptic Transmissiono 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 bodyo 2. Storage in vesicles packaged into these vesicles using active transport neurotransmitters highly concentrated in the vesicleso 3. Release across