Neurophysiology:Part IILet’s ReviewSlide 3Slide 4Slide 5Slide 6Slide 7Slide 8Otto Loewi’s ExperimentDiscovery of NeurotransmittersNitric Oxide: The Strangest ………..Neurotransmitter?!?Our Goal Today Is To Attempt to Answer the Following Questions:Generally Speaking….Viagra’s SecretSlide 15Neurotransmitters(Definition)Types of NeurotransmittersNeurotransmitter: Chemical StructuresProduction of NTsNeuropeptidesNeuropeptide SynthesisHow Do Newly Synthesis Proteins (NTs) travel to the Axon Terminal So Quickly?What is Retrograde transport?IonotropicIonotropic with InhibitoryExcitatory Cholinergic Synapse (Example of Excitatory NT w/ Ionotropic EffectsSynaptic TransmissionSlide 28Inhibitory GABA-ergic SynapseExcitatory Adrenergic SynapseExcitatory Adrenergic Synapse/Metabotropic EffectsNeuromodulatorsPostsynaptic Potentials- EPSPPostsynaptic Potentials- IPSPSlide 35Slide 36Slide 37Slide 38Slide 39How Cocaine Causes EuphoriaFrom Synapse to Receptor SiteNeurophysiology:Part IILecture IILet’s ReviewWhat does an action potential “spike” look like? When is depolarization, neutralization ? Hyperpolarization? What is happening to ion channels at these times? What is happening the neuron at this time?Compare and contrast the speed of propagation in varying axons with respect to thickness and with respect to myelination.Axonsomatic, axonaxonatic and axondendritic: a diagram.NEUROTRANSMITTERSOtto Loewi’s ExperimentDiscovery of NeurotransmittersHistological observations revealed gap between neurons (synaptic cleft)Otto Loewi (1873-1961) demonstrated the function of neurotransmitters flooded exposed hearts of 2 frogs with salineRepeatedly stimulated vagus nerve ---Slowed 1st heart slowedremoved saline from that 1st frog heart and transferred it to the second frog heart. The second frog heart decreased its beat. Loewi concluded that the nerve released a chemical --- “vagus substance”  later renamed acetylcholineNitric Oxide: The Strangest ………..Neurotransmitter?!?Nitric oxide (NO) is a gas. It is highly reactive; that is, it participates in many chemical reactions. (It is one of the nitrogen oxides ("NO") in automobile exhaust and plays a major role in the formation of photochemical. In high concentrations this is a poisonous gas! NO is now known to be a neurotransmitter! Huh?? Yup. So, then, what is criteria for neurotransmitter you ask?Our Goal Today Is To Attempt to Answer the Following Questions: What is a Neurotransmitter?How are Neurotransmitters classified?How are Neurotransmitters synthesized in the body?Compare and contrast the effects of Neurotransmitters which are one of three : ionotropic, metabotropic or modulatory.Generally Speaking….Neurotransmitters, along with electrical signals, are the “language of the nervous system!More than 50 neurotransmitters have been identified but we know there are over 100 in existence. Released by the PRESYNAPTIC neuron from vesicles, usually, one or two per neuron, but each neuron can receive many kinds. Neurotransmitters are classified chemically and functionally.Viagra’s SecretNitric oxide functions as a signaling molecule that tells the body to make blood vessels relax and widen. This physiological reaction is important when the body needs more blood--the brain signals to the blood vessels near the arms, for example, when the arms need more blood supply for muscle movement or for warmth. Thus, NO works as a signaling molecule in the cardiovascular system, the nervous system, and in other tissues.The brain sends signals to NANC cells in the artery. The NANC cells release nitric oxide (NO). Nitric oxide acts as a signaling molecule and stimulates an enzyme called guanylate cyclase in nearby cells. The guanylate cyclase converts a chemical called GTP into another chemical called cGMP. cGMP causes muscles in the walls of the arteries to relax. This relaxation increases blood flow. Meanwhile, PDE is decomposing the cGMP and turning it back into GTP. There is a cycle -- guanylate cyclase turns GTP into cGMP, and PDE turns cGMP into GTP. Nitric oxide turns the cycle on.Neurotransmitters(Definition)are chemicals that are used to relay, amplify and modulate electrical signals between one neuron and another .It is synthesized endogenously, that is, within the presynaptic neuron It is available in sufficient quantity in the presynaptic neuron to exert an effect on the postsynaptic neuron; Externally administered, it must mimic the endogenously-released substance; A biochemical mechanism for inactivation must be present.Types of NeurotransmittersAcetylcholineformed from acetic acid and cholineMOST NTs are classified in one of the following 3 groups: Notice that each is formed from amino acids.Amino acids GABA glycine aspartic acid glutamic acid Monoaminessynthesized by replacing –COOH in amino acids with another functional groupCatecholamines  (Epinephrine, Norepinephrine and Dopamine)Indolamines (serotonin and histamine)Neuropeptides long chains of amino acids ( 2 to 40) Continued on next slide.Neurotransmitter: Chemical StructuresProduction of NTsNeuropeptidesChains of 2 to 40 amino acidsStored in axon terminal as larger secretory granules (called dense-core vesicles)Act at lower concentrationsLonger lasting effectsSome released from nonneural tissuegut-brain peptides cause food cravingsSome function as hormonesmodify actions of neurotransmittersTo date there are around fifty peptides, which are known to act as neuronal messengers.Substance P, gastrin, cholecystokinin (CCK) neuropeptide Y, enkephalin and endorphoin B dynorphin are just a few.Neuropeptide SynthesisPeptides are essentially Proteins and require a sequence of amino acids.We are basically talking about transcription and translation for synthesis. Sorting and packaging ( ER and Golgi)Neuropeptides are produced in the soma and transported to terminal where they are stored in vesicles.How Do Newly Synthesis Proteins (NTs) travel to the Axon Terminal So Quickly? Micotubules and motor proteins are needed for Vesicles quickly to the axon terminal or synaptic knob. Newly synthesized membrane and secretory proteins destined for the axon travel by fast anterograde transport.What is Retrograde transport?This is transport in the opposite direction.Used mainly to transport