Synaptic transmission

Transcription

1 Outline Synaptic transmission Sompol Tapechum M.D., Ph.D. Department of Physiology Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. 2 Structure of synapse Modes of synaptic transmission Electrical synapse Chemical synapse Neurotransmitters Definition Classification Mechanisms of synthesis, storage, release, action and inactivation Neurotransmitter Receptors Ionotropic receptors Metabotropic receptors Postsynaptic potential Excitatory postsynaptic potential (EPSP) Inhibitory postsynaptic potential (IPSP) Fast synaptic transmission Slow synaptic transmission References Cobra venom Botulinum toxin 3 4 Synapse Synapsis (Gr) = union or association Synapse = Specialized zone of contact at which one neuron communicates with another Neuronal Synapses Neuro-effector Synapses: Neuromuscular junction 5 Michael J Fox Parkinson s disease John Nash Schizophrenia 6 Neuronal synapse Neuromuscular junction

2 Structure of Neuronal Synapse Modes of Synaptic transmission Postsynaptic neuron Postsynaptic neuron No structural connection Chemical messengers Neurotransmitter Chemical synapse Structural connection Gap junction channels Ions Synaptic cleft Electrical synapse 7 8 Evidence of chemical transmission Chemical synapses Loewi s experiment (1921) demonstrating the Principle of Chemical Transmission Communication using neurotransmitters released from presynaptic neurons Vagusstoff released by stimulation of vagus nerve slowed heart rate Synaptic cleft (20 nm) Pre Post Postsynaptic cell 9 10 Neurotransmitters Classes of neurotransmitters 1. It is synthesized in the neuron. 2. It is present in the presynaptic terminal. 3. It is released by a neuron when the the neuron is stimulated. 4. After released, it exerts a defined action on postsynaptic neuron or effector organ. 5. A specific mechanism exists for removing it from the site of action. 6. Exogenous administration mimics the endogenously released transmitter exactly. Small molecule neurotransmitters or classical neurotransmitter synthesized in presynaptic terminal stored in small clear vesicles Acetylcholine Biogenic amines: dopamine, adrenaline, noradrenaline, setotonin, histamine Amino acids: glutamate, glycine, GABA Purines: adenosine, ATP Neuroactive peptides synthesized from mrna in soma of presynaptic neurons stored in large dense-cored vesicles Substance P, VIP, Somatostatin, cholycystokinin, enkephalin Gaseous: NO, CO 11 12

3 Neutransmitter synthesis Norepinephrine synthesis Precursor peptide Active peptide neurotransmitter Classical neurotransmitters Synthesized in terminal Packaged in small vesicles Small clear vesicles Large dense core vesicles Neuropeptide Synthesized in cell body Packaged in large vesicles Transport to terminal Precursor molecule Synthetic enzyme Neurotransmitter molecule Transporter protein Mechanism of Neurotransmitter release Neurotransmitter release and action action potential postsynaptic potential voltage-gated Ca 2+ channels exocytosis (SNAREs) postsynaptic receptors 15 Active zone = the site where neurotransmitter is released = contains Ca ++ channels and proteins regulate release ω-conotoxin Botulinum toxins Black widow spider Clostridium bacteria Inhibit voltagated Ca 2+ channel Destroy presynaptic protein (SNAREs protein) 16 Postsynaptic potential (PSP) Excitatory postsynaptic potential (EPSP) PSP is local potential Graded response Can be excitatory (EPSP) or inhibitory (IPSP) Passive or electrotonic conduction Can be summated Postsynaptic membrane depolarization Ex. Na + influx If threshold reached, action potential generated. Threshold 17 18

4 Inhibitory postsynaptic potential (IPSP) Summation of PSP (1) Postsynaptic membrane hyperpolarization Ex. Cl - influx Spatial summation When activity is present in more than one synaptic knob at the same time Threshold Temporal summation When repeated afferent stimuli cause new PSPs before previous PSPs have decayed Postsynaptic receptors Ionotropic receptor Postsynaptic receptor = transmembrane protein at postsynaptic membrane capable of binding specific neurotransmitter. Neurotransmitter binding to postsynaptic receptors causes membrane potential changes in postsynaptic cells (postsynaptic potential; PSP). by acting directly or indirectly on ion channels. Direct gating Indirect gating Receptors is ligand-gated channels Consist of two parts Neurotransmitter binding site Ionotropic receptor Fast transmission Metabotrotropic receptor Slow transmission Pore eg. Nicotinic ACh receptors, NMDA, GABA A Postsynaptic response: Fast (fast EPSP or Fast IPSP) Metabotropic receptor Fast and Slow synaptic transmission Activation of GTP-binding protein (G-protein) G-protein activates ion channels through G-protein subunit Second messenger eg. camp, IP 3, Ca 2+ Postsynaptic response: Slow (slow EPSP or slow IPSP) Examples: Adrenergic receptors Muscarinic Ach receptors Serotonin receptors Metabotropic glutamic receptor Fast synaptic transmission generates action potential Slow synaptic transmission modified cell excitability Control cell excitability Modulates fast synaptic transmission Modulates spontaneous activity Close K+ channels ==> Slow EPSP Open K+ channels ==> Slow IPSP 23 24

5 Termination of neurotransmitter effects Psychostimulants: Cocaine and amphetamine Diffuse away Reuptake Dopamine, Norepinephrine Enzymatic degradation Acetylcholine Acetylcholine esterase Catecholamine Monoamine oxidase (MAO) Catechol-o-methyl transferase (COMT) Cocaine Amphetamine Block reuptake Competitive inhibitor for reuptake Displacement of neurotransmitters from vesicles Synaptic plasticity Mechanism of synaptic plasticity The ability to change strength of synaptic transmission The effect can be short-term or long-term Post-tetanic potentiation Short-term Increase intracellular Ca 2+ in presynaptic terminal as a result of repetitive stimulation Long-term Activation of intracellular cascades as a results of increase intracellular Ca 2+ in postsynaptic terminal Increase protein synthesis Increase receptor expression Increase number of synapses Short-term Long-term Conclusion Structure of synapse Synaptic transmission is mainly chemical transmission. The processes of synaptic transmission consist of synthesis, storage, release, receptor binding and termination. Release of neurotransmitter requires Ca 2+ and SNAREs protein Postsynaptic potential can be either excitatory or inhibitory and fast or slow PSP. The most important factor determining the postsynaptic response is the postsynaptic receptors. The response of postsynaptic cell depends on the integration of all the incoming signal converged to that cell. Spatial and Temporal summation Synaptic transmission can be modified functionally or structurally and short-term or long-term