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Cell to cell communication in the nervous system • • • • • • • • The synapse Electrical synapse Chemical synapse Role of calcium “neurocrines” Receptors Post-synaptic responses Terminating synaptic neurotransmission The synapse • Presynaptic cell • Synaptic cleft • Postsynaptic cell Electrical synapse •Rapid •Few cns neurons, glia •Cardiac muscle •Smooth muscle Chemical synapse •Releases neurotransmitter •Synaptic vesicles •Docking The effect of calcium on synaptic neurotransmission •Action potential •Voltage gated Ca++ channel •Synaptic vesicle docking •Neurotransmitter exocytosis •Ligand/receptor binding on postsynaptic cell. Substances released by neurons • paracrines – Neurotransmitters (act at synapse) and neuromodulators (act away from synapse) – Neurohormones released into blood • Autocrines, same signaling molecules act on the cell that releases them Examples of neurotransmitters • Acetylcholine- neuromuscular jn and CNS • Amino acids – glycine, glutamate, GABA • amino acid derived amines – epinephrine, norepinephrine, dopamine, serotonin • Peptides – substance P, endorphins • Purines - ATP • Gases – nitric oxide Multiple neurotransmitter receptors • Ionotropic – ligand gated channels • Metabotropic – ligands activate 2nd messengers and/or G proteins that gate the channel Ionotropic receptor Metabotropic receptor Multiple neurotransmitter receptors: subtypes • Cholinergic – nicotonic (neuromuscular jn), ligand gated – Muscarinic, 5 subtypes, G protein and 2nd messenger linked Adrenergic receptors • Adrenergic – alpha and beta – Linked to G proteins and 2nd messengers – Alpha and beta are linked to different G proteins and different 2nd messengers Glutaminergic receptors • • • • Important in the CNS Named for agonists AMPA receptors – ligand gated NMDA receptors – bind ligand (glutamate) but channel opens during depolarization Glutamate Receptors NMDA receptor AMPA receptor Duration of post-synaptic response • Fast synaptic potential, usually from ionotropic receptors. – A channel is opened – Synaptic potential can be depolarizing or hyperpolarizing • Slow synaptic potential – G proteins and 2nd messengers – Slower and lasts longer Neurotransmitter activity is quickly terminated • Acetylcholine is broken down by acetylcholinesterase Neurotransmitter activity is terminated • Norepinephrine is actively transported back to the pre-synaptic axon • CNS neurotransmitters (amines, peptides, amino acids) move into circulation or transported to pre-synaptic terminal.