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Name _________________________________________________ Modeling Chemical Synapses A synapse is the place where signals are transmitted from a neuron, the presynaptic neuron, to another cell. This second cell may be another neuron, muscle cell or glandular cell. If the second cell is a neuron, it is called the postsynaptic neuron. The majority of synapses are chemical synapses which function by releasing a chemical called a neurotransmitter from the presynaptic neuron. Over 50 different neurotransmitters have been identified with another 50 suspected of being neurotransmitters. These neurotransmitters act to excite or inhibit postsynaptic cells by binding to specific receptor proteins embedded in the postsynaptic cell. Depending on the receptor, the same neurotransmitter may have excitatory effects at some synapses while having inhibitory effects at others. For example, acetylcholine excites skeletal muscle cells but inhibits cardiac muscle cells. In this simulation you will determine how excitatory and inhibitory neurotransmitters alter the release of dopamine from the last neuron in a series. Using your computer or your textbook, complete the following table. Neurotransmitter Role in the body acetylcholine dopamine GABA (gamma-aminobutyric acid) glutamate norepinephrine serotonin Operation of the nervous system is dependent on the flow of information through chains of neurons functionally connected by synapses. The neuron conducting impulses toward the synapse is the presynaptic neuron, and the neuron transmitting the signal away from the synapse is the postsynaptic neuron. Chemical synapses are specialized for release and reception of chemical neurotransmitters. For the most part, neurotransmitter receptors in the membrane of the postsynaptic cell are either 1.) channel-linked receptors, which mediate fast synaptic transmission, or 2.) G protein-linked receptors, which oversee slow synaptic responses. Channel-linked receptors are ligand-gated ion channels that interact directly with a neurotransmitter and are called ionotropic receptors. Alternatively, metabotropic receptors do not have a channel that opens or closes but rather, are linked to a G-protein. Once the neurotransmitter binds to the metabotropic receptor, the receptor activates the G-protein which, in turn, goes on to activate another molecule. Part 1 – Cholinergic Synapse Model the ionotropic cholinergic synapse shown below. Be sure to label all of the following: voltage-gated sodium channel, voltage-gated potassium channel, neurotransmitter, synaptic vesicle, presynaptic cell, postsynaptic cell, potassium leaky channel, sodium-potassium pump, synaptic cleft, acetylcholine receptor, acetylcholinesterase, calcium channel, SNARE proteins. Step 1 - Action potential arrives at the terminal end of the presynaptic cell. Step 2 - Calcium channels open in the presynaptic axon terminal. Open the calcium channels (red) and move some calcium ions to the interior of the neuron. Calcium ions bind to synaptotagmin. Step 3 - SNAP/SNARE proteins interact to bring the vesicle in position to fuse with the cell membrane. Acetylcholine is released. Move the synaptic vesicle to the terminal end of the neuron. Step 5 - Ion channels open in the postsynaptic membrane. The acetylcholine receptor opens to allow sodium ions to follow their concentration gradient into the postsynaptic cell. Depolarization of the postsynaptic cell occurs and an action potential may be generated in the post synaptic cell. Step 4 - Acetylcholine binds to postsynaptic receptors. Acetylcholine traverses the synaptic cleft to bind to the acetylcholine receptor on the postsynaptic membrane. Step 6 - Termination of acetylcholine effects. The enzyme acetylcholinesterase breaks the neurotransmitter down into acetic acid and choline. An uptake receptor transports choline back into the presynaptic cell for use in the synthesis of more acetylcholine in the presynaptic cell. Learning Check: A. Identify the ion that triggers the SNAP/SNARE proteins to cause the synaptic vesicle to “kiss and run”. ____________ B. What molecule is released into the synaptic cleft in this model? _________________________ C. Why is it important that acetylcholinesterase is present in the synaptic cleft? ________________ _______________________________________________________________________________ D. What happens in the post synaptic cell when acetylcholine binds to the receptor? ____________ _______________________________________________________________________________ E. Identify the cholinergic synapse modeled here as excitatory or inhibitory. Explain your choice. ________________________________________________________________________________ F. Brainstorm ways in which the transmission in a cholinergic synapse could go wrong. 1. _________________________________________________________________________ 2. _________________________________________________________________________ 3. _________________________________________________________________________ Part 2 – Dopaminergic Synapse Model the metabotropic dopaminergic synapse shown below. Be sure to label all of the following: voltage-gated sodium channel, voltage-gated potassium channel, dopamine, synaptic vesicle, presynaptic cell, postsynaptic cell, potassium leaky channel, sodium-potassium pump, synaptic cleft, G-protein coupled receptor, calcium channel, dopamine transporter, vesicular transporter, SNAP/SNARE proteins. Repeat steps 1-3 as before, but use dopamine as the NT. Step 4 - Dopamine traverses the synaptic cleft to bind to the extracellular domain of the metabotropic receptor in the postsynaptic membrane. The intracellular domain of the metabotropic receptor binds to G-proteins. The G-protein has three subunits: alpha(α), beta(β), and gamma(γ). Step 5 - Bound dopamine activates the metabotropic receptor. The α subunit dissociates from the βγ complex. The α subunit triggers a signal cascade that ends in the opening of ion channels, depolarizing the postsynaptic cell. Step 6 - The effects of dopamine are terminated when dopamine is removed from the synaptic cleft by the dopamine uptake transporter and returned to the vesicle. Learning Check: A. Identify the dopaminergic synapse modeled here as excitatory or inhibitory. Explain. ______________________________________________________________________________ B. Describe how an ionotropic receptor differs from a metabotropic receptor. ______________________________________________________________________________ ______________________________________________________________________________ C. Brainstorm ways in which the dopaminergic synapse transmission could go wrong. 1. ______________________________________________________________________ 2. _______________________________________________________________________ 3. _______________________________________________________________________ Let’s look at a case study of the Beery Twins – dopamine deficiency Part 3 – GABAergic Synapse Model the GABAergic synapse shown below. Be sure to label all of the following: voltage-gated sodium channel, voltage-gated potassium channel, GABA, synaptic vesicle, presynaptic cell, postsynaptic cell, potassium leaky channel, sodium-potassium pump, synaptic cleft, GABA receptor, calcium channel, SNAP/SNARE proteins. Model steps 1-4 as you did with the cholinergic synapse, but use GABA as the NT. Step 5 - Ion channels open in the postsynaptic membrane. The GABA receptor opens to allow chloride ions (Cl-) to follow their concentration gradient into the postsynaptic cell. Hyperpolarization of the postsynaptic cell occurs inhibiting the generation of an action potential. Step 6 - High-affinity transporters terminate the action of GABA by returning it to the presynaptic neuron for reuse. Learning Check: A. Identify the GABAergic synapse as ionotropic or metabotropic. Explain. ______________________________________________________________________________ B. Why is the GABAergic synapse considered inhibitory? _________________________________ _______________________________________________________________________________ Project due date __________________________________ Each table will be assigned a different drug that somehow interferes with synaptic transmission. Your job is to research the drug’s action on the neurons/synapses and the long-term effects, create a model using the appropriate synapse type from the Synapse Kit. Drugs to choose from: caffeine, tetanus toxin, methamphetamines, cocaine, sarin gas, alcohol, or propofol (Diprivan) Construct your own “informational placemat” that explains the normal vs. the drug effects at the synapse level and the effects on body systems. Use your own photographs of your model and others on your placemat. If time permits, your group will present your model and drug effects to the class.