Handout Lecture 4 Nervous System 2025 PDF

Lecture 4 PHCL2610 Nervous System Ana Maria Oyarce Ph.D. Department of Pharmacology – HEB280C Office hours: TBD or by appointment Phone: (419)383-1919 Email: [email protected] 1  Topics  Synaptic T...

Lecture 4 PHCL2610 Nervous System Ana Maria Oyarce Ph.D. Department of Pharmacology – HEB280C Office hours: TBD or by appointment Phone: (419)383-1919 Email: [email protected] 1  Topics  Synaptic Transmission  Neurotransmitters  Receptors  Postsynaptic Potentials Material Vander’s Human Physiology 16th Edition. Copyright 2023 Chapter 6. Section C: Synapses 2 3  Synaptic Transmission  Synaptic transmission is the biological process by which a neuron communicates with a target cell (neuron or tissue cell) across a synapse  A synapse or synaptic cleft is a microscopic space formed between two neurons or a neuron (nerve terminal) and a target cell 4 5  Location of Chemical Synapses  Presynaptic neurons can interact with postsynaptic neurons at three locations Axodendritic synapse Axosomatic synapse Axoaxonic synapse is between the axon is between the axon is between the and dendrite and cell body axons 6  Types of Synapses Electrical synapse  Plasma membranes of presynaptic and postsynaptic cells are joined by gap junctions (channels)  Gap junctions allow direct diffusion of ions  Electrical synapses are relatively uncommon Chemical synapse Presynaptic neurons release neurotransmitters (NTs) from their axon terminals NTs bind to receptors on post-synaptic neurons They can be inhibitory or excitatory depending on the neurotransmitter and receptor They are the most common synapse 7  Mechanisms of Signaling at a Chemical Synapse Nerve impulse Production of action potential change in membrane potential flow of ions Synaptic transmission Release of neurotransmitters (NTs) at the synapse NTs are stored within sacs called synaptic vesicles at the axon terminal 8  Neurotransmitters  Neurotransmitters are chemical messengers  An excitatory transmitter promotes an action potential in the receiving neuron  An inhibitory transmitter prevents the formation of an action potential  Effect will depend on the receptor to which the NT binds to 9 Criteria Defining Neurotransmitters 10  Removal of Neurotransmitter NT removal ensures that the signal does not overstimulate the post-synaptic cell Removal mechanism depends on the NT 1. Reuptake  NT is transported back into the presynaptic terminal of neuron for reuse or metabolism  Transport into nearby glial cells where they are degraded 2. Enzymatic transformation into inactive substances  At the synaptic cleft (acetylcholine)  Inside the cells (norepinephrine) 3. Diffusion away from the receptor site at the synapse 11  Neurotransmitter Receptors  Neurotransmitter released into the synaptic cleft binds to ligand-gated receptors to produce an effect Two categories 12  Ionotropic Receptors  They are ligand-gated ion channels → channels are modulated by the binding of a neurotransmitter (ligand)  Fast neurotransmission rapid effect  Two functional domains:  An extracellular NT binding site  A membrane spanning domain that forms an ion channel (K+, Na+, Cl- & Ca2+)  Effect: depolarization (excitatory) or hyperpolarization (inhibitory) depending on channel  Examples: GABA (Gamma-aminobutyric acid), Acetylcholine, Glycine and serotonin Acetylcholine binds to the nicotinic receptor 13 Metabotropic Receptors Slow neurotransmission → slow response G-protein coupled receptors (GPCRs; 7 transmembrane domains) they are indirectly linked to ion-channels The ion channel is not part of the receptor structure Examples: Glutamate, acetylcholine, monoamines (epinephrine and norepinephrine) 14  How Does A GPCR Work? 1. NT binds to receptor  It activates receptor changes its conformation  Protein G gets activated NT 3. Effect on the Effector  The activation or inhibition of the effector will depend on the type E of G protein G  Effect in the cells or tissues G  Second messenger production G  Channel activation 2. G protein is activated  It dissociates from receptor  G protein binds to effector 15 GPCR and Ion Channel System 16  Activation of G Proteins  bg subunits  bg subunits can always stay activate an effector 1.Ligand binds together as in same systems to receptor (*) complex 2. Exchange of 3.Dissociation 4. Dissociated subunits bind to GDP for GTP of a from bg effectors on a subunit subunits  Activation or inhibition of effectors  Most common effect is from the binding of a subunit to E 17 Formation of Inactive State of G Proteins E 6. Formation of inactive state 5. Hydrolysis of GTP following  a and bg come together and form activation of effectors the initial complex or trimeric G  GTPase activity in a subunit protein hydrolyses GTP to GDP  The initial complex binds to GPCR  Both a and bg dissociate from effectors 18 GPCR and Direct Ion Channel Activation 1. NT binds to receptor 4. The bg subunits bind 3. as subunit binds and activates the effector H and activates the (K+ Channels) effector (Ca2+ channel) E as E b 5. Open K+ g as b 4. Open Ca2+ channels g channels b as g 2. G protein is activated  It dissociates from receptor 19 G Proteins and Ion Channels 20 GPCR and Indirect Ion Channel Activation Activation of calcium and sodium channels by phosphorylation PKA= Protein Kinase A 21 Postsynaptic Potentials 22 Excitatory Postsynaptic Potential (EPSP)  Slight depolarization due to increased permeability to primarily Na+ and to a lesser extent Ca+2  EPSP increases the likelihood of producing an action potential 23  Inhibitory Postsynaptic Potential  IPSP= slight hyperpolarization resulting from increased permeability to Cl- or K+  Generation of an action potential is more difficult than usual 24  Postsynaptic Potentials Postsynaptic potentials are graded Small local (small region) changes in membrane potential The magnitude depends on stimulus → number of activated channels Summation is the process by which graded potentials are added together Net result is a larger depolarizing or hyperpolarizing graded potential 25  Summation at a Postsynaptic Neuron  Summation is the additive effect of several electrical impulses 26