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SSN 1 WORKSHEET 2 2/4/02 SYNAPTIC TRANSMISSION (Chapters 10, 11, 12, 14) 1. There are two types of synapses, electrical and chemical. If you inject current into the presynaptic cell, through which channels will it pass in the electrical synapse? Chemical synapse? How does transmission across each type of synapse result in an action potential in the postsynaptic cell? [See figure10-1, p 176, and text, p176-177] Remember for both synapses that the current will always travel in the path of least resistance to its flow. The least-resistant paths are different for each synapse. Electrical: some escapes through resting ion channels [remember that when we talk about current, we are also thinking about ion movement], others through gap junctions (direct low resistant, high conductance path) into postsynaptic cell. There, more escapes out of the ion channels. If depolarization exceeds threshold, an action potential will be generated. Chemical: ALL through ion channels in presynaptic cell (much less resistance than crossing the external membrane of the postsynaptic cell to get in). But, this results in depolarization of the cell which activates neurotransmitter release from synaptic vesicles, which can then travel across synaptic cleft to postsynaptic cell, bind to receptors*, open ion channels, change membrane potential, and if depolarization exceeds threshold, an action potential will be generated. 1b. Describe the difference between ionotrophic and metabotrophic receptors and give one example of each. IONOTROPHIC - receptor and ion channel in same macromolecule—transmitter binding opens channel. One example is the Nicotinic Ach receptor found at the neuro-muscular junction. Other examples: Glutamate, Glycine, GABA, … METABOTROPHIC - coupled to second messengers (eg. G proteins) that indirectly influence channel opening. Examples: Muscarinic Ach receptor; Adrenergic receptors 2. Functional properties of the electrical and chemical synapses A. Which synapse is used in fast, defensive reflexes in the aplysia? Why? Electrical because they’re faster—there is a rapid coupling between pre and post-synaptic cells. In chemical, it takes time for the neurotransmitter to be released, travel across, bind to receptor, etc., so it’s slower. B. Which synapse is used when one wants amplification of the signal? Why? Chemical. This is because the presynaptic cell releases a large amount of neurotransmitters that can combine with many postsynaptic receptors and open many ion channels. C. Which synapse is used when it is necessary for a large population of neurons to be acting as a single unit? Why? (p. 180) Electrical. Because current flows across the membranes of all electrically coupled cells at the same time, several small cells can act coordinately as one large cell and will fire synchronously. This is similar to the cardiac muscle cells firing in sequence. [Also, because the cells are coupled, their total resistance is smaller than the resistance of a single cell, but a larger current is needed to depolarize them to threshold. Delta V = Delta I x R] D. Which synapse allows for transmission from a smaller cell to a larger cell? Chemical (ie, this happens in the NMJ). In the chemical synapse a small amount of neurotransmitter can create a large post synaptic depolarization depending on the number of post synaptic receptors and ion channels as well as the half life of the neurotransmitter in the synaptic cleft. In electrical synapses, the signal must go from a larger cell to smaller cell. This is because (p177) the current that depolarizes the postsynaptic cell is generated directly by the voltage-gated ion channels of the presynaptic cell. Thus these channels must not only depolarize the presynaptic cell, but must generate enough ionic current to produce a potential change in the postsynaptic cell. For such a large current to be generated, the presynaptic cell must have a lot of ion channels, and therefore, must be relatively large. The postsynaptic cell must be relatively small because, as seen in Ohm’s law (∆ V = ∆I x Rm), in response to a given current (∆I), there will be a greater change in potential (∆V) if there is a higher input resistance, and small cells will have a larger resistance than a larger cell. 3. Stimulation of which of the following two nerves is more likely to cause a post synaptic action potential: 1) An single excitatory CNS neuron 2) a motoneuron at the NMJ? The amplitude of the end-plate potential in a muscle cell is very large – usually stimulation of a single motor cell produces a synaptic potential of about 70mV. This is usually large enough to activate voltage-activated Na+ channels to propagate an action potential. In contrast, CNS presynaptic neurons produce postsynaptic potentials of less than 1mV in amplitude, so input from multiple presynaptic neurons is necessary to generate an action potential in the CNS. (p 190) 4. The reversal potential at the motor end-plate is 0mV. Assuming virtually all channels at the end plate to be Ach-gated channels, what specific property of Achgated channels does this value for resting potential tell us about? The reversal potential is the potential at which the net ionic current across the membrane is zero. It is a way of experimentally measuring the EEPSP (the battery resulting from the concentration gradients of ions conducted through a Ach-gated channels at the end-plate). According to the equation IEPSP = gEPSP X (Vm – EEPSP), if the influx of Na+ were solely responsible for the end-plate potential, the reversal potential would be +55mV (all current at that point would be 0. Since the reversal potential is 0mV (which represents a weighted average for the equilibrium potentials of BOTH Na+ and K+), Ach-gated channels must be permeable to BOTH of these ions. This permeability to two different ions is a property that separates Ach-gated channels from many of the other voltage-gated channels (detailed explanation on p 191-192). 5. What are some differences between the Ach gated channels and the voltage gated channels at the post synaptic junctional fold? The Ach channel is chemically activated and permeable to both Na and K through he same pore. Also in the voltage gated channels Na+ influx is regenerative (increased depolarization by inward Na+ current causes more voltage-gated Na+ channels to open), while only the amount of Ach available determines ion flux across Ach-gated channels. (p 196-197) 6. What are the two major ways that the NMJ (a peripheral synapse) differs from the synapses in the CNS? What are temporal and spatial integration, and why are they needed in the CNS, but not the NMJ? 1. There are only excitatory post synaptic potentials in the NMJ. The CNS has inhibitory post synaptic potentials which hyperpolarize the postsynaptic cell (whereas the activating postsynaptic potentials, EPSP, depolarize the cell) 2. In the NMJ, the release of Ach from one presynaptic cell is sufficient to react with Ach receptors in the post synaptic cell and cause sufficient depolarization to produce an action potential. However, in the CNS, a signal from one sensory neuron is not sufficient to produce an action potential in the postsynaptic cell. In fact, the EPSP is about 1mV, whereas about 10mV are needed to reach threshold. Therefore, temporal and special integration are needed to reach the threshold 10mV potential. Temporal integration or summation is when the presynaptic neuron signals the postsynaptic neuron with consecutive action potentials that occur one after the other quickly, resulting in EPSPs of increasing magnitude in the postsynaptic cell until threshold is reached. Spatial integration or summation is when inputs from many presynaptic neurons converge on one post-synaptic neuron and the resulting EPSPs are summed to create an action potential. The relative importance of these EPSPs depend on where they occur on the dendritic tree and how close they are to the axon hillock. (p. 222-223) 7. Excitation in the CNS A. Name the primary excitatory neurotransmitter in the CNS: Glutamate B. What are the three ionotrophic glutamate receptors and what ions pass through them? NMDA, AMPA, and kainite (the last 2 are sometimes considered “non-NMDA” receptors). All 3 are Na and K channels. NMDA also allows Ca through. C. Explain the unique features of NMDA receptors. Binds glutamate. The NMDA receptor has the highest Ca conductance, and a binding site within the channel for extracellular Mg. At Vm< -70mV (V rest) the NMDA receptor is blocked by Mg, and only the other two channels are available for fast depolarization. Depolarization of the cell removes the block, allowing an influx of Ca through the NMDA receptor when glutamate binds. Ca binds intracellular proteins and is important in long term potentiation and memory in the hippocampus. Stroke can cause cell damge, Ca release, and positive feedback and excitotoxicity via the activation of cell proteases and phospholipases, leading to cell degradation. 8. Inhibition in the CNS A. Name the primary inhibitory neurotransmitters in the CNS: Glycine, GABA B. Which ion channels do these NTs open? Chloride C. How does the opening of these channels inhibit the postsynaptic cell? In a normal cell, there is much more Cl- ion outside the cell than inside, and thus there is a favorable concentration gradient for Cl- to enter the cell. In a typical neuron the resting potential (-65mV) is slightly more positive than the Ecl (-70mV). Thus, at the resting potential the electrochemical driving force on Cl- (Vm-Ecl) will be positive. Therefore, if a Cl- channel opens, Cl- will rush inside the cell, making the cell more negative, and resulting in hyperpolarization. [The synaptic current can be calculated from: Iepsp=Gipsp (Vm-Ecl)] D. What is hyperekplexia (familial startle disease) and what causes it? Inhibitory channels include GABA and glycine-activated Cl- channels. Familial startle disease results from a missense mutation in the alpha-subunit of the glycine receptor which decrease the function of the glycine receptor. Therefore, the afflicted individual lacks sufficient inhibition in the spinal cord and stimuli that shouldn’t cause a response do. This leads to abnormally high muscle tone and exaggerated responses to noise. 9. How does Ca+-calmodulin-dependent kinase play a role in synaptic transmission.? Ca influx from voltage gated calcium channels at the presynaptic bouton activate CAM Kinase, which phosphorylates synapsins. The synapsins cause vesicle fusion and release of neurotransmitter. (p 270) 10. If you had a resting potential in a presynaptic neuron that was hyperpolarized compared to its usual level at –90mV, would neurotransmitter release increase, decrease, or stay the same when an action potential arrives? It would decrease, since, at a hyperpolarized presynaptic potential, there is a decreased slow constituitive influx of Ca+.(p 274)