Week 1 - 3/21 Lecture 8, 9, 10
Recall that Erev is defined by what two properties?
(1) the permeability to various ions (2) the concentration gradient of those permeant ions.
What experiment gave evidence to synaptic release being strongly [Ca] dependent? What kind of binding was implied?
*Used low Ca levels As the [Ca2+] is increased, the amplitude of the EPP increases dramatically - as the 4th power of [Ca2+]. This steep dependence on concentration implies cooperative binding of multiple Ca2+ ions at the site controlling vesicle release Ca changes the probability of events occurring synchronously - affects how many quanta will be released; it DOES NOT change the size of the quanta
T/F: Trauma to the brain causes inhibition of glutamate release
False - Brain injury from trauma, seizures, or reduced blood flow (stroke) causes an excessive release of Glu and exitotoxic damage to neurons.
T/F: All receptor types and subtypes within a family will be composed of the same subunits.
False - GABAb receptors, for example, can have differentiating subunits in different areas of the nervous system
T/F: In trying to understand the action of channels, voltage is measured. What technique is used to do this?
False - current. Because current is the flow of ions through the channel. The current-voltage relationship for a postsynaptic ionotropic receptor is measured with the voltage-clamp technique - to set the postsynaptic potential at a fixed value and observe the current elicited by application of transmitter. These experiments are performed most easily at the neuromuscular junction, wherein the muscle fiber is voltageclamped and the endplate current (EPC) is measured for the nAChR
T/F: GABAbR signalling is excitatory. T/F: GABAbR signalling is ionotropic. T/F: GABAbR is found in the brain
False - inhibitory; False - metabotropic; True
T/F: For a potential to be excitatory, Erev must be below threshold. T/F: For a potential to be inhibitory, Erev must be above threshold.
False - just the opposite; False - just the opposite
T/F: If membrane potential depolarizes and reversal potential is more negative than threshold, there will be an excitatory response. Explain.
False - the tendency to fire will be inhibited. This is demonstrated in the third panel from the left. This happens because although the potential is depolarizing, once Erev is reached or slightly surpassed, conduction will occur in such a way as to "pull" the potential back to Erev, so that threshold is not met and an AP is not fired.
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What two conditions must be met in order for NMDA to be activated as a coincidence detector?
1) Glutamate binds 2) Must be depolarization to knock off the Mg
What three characteristics define the electrical synapse (speed, direction, kind of electrical activity produced)?
1) Synaptic transmission is extremely fast, much less than the 1-2 msec of a chemical synapse (Fig 24) 2) Synaptic transmission can be bidirectional (i.e. either direction, pre → post or post → pre) and may occur for subthreshold electrical transients (i.e. without action potentials). 3) Electrical synapses promote synchronized electrical activity among a population of neurons (Fig 25).
What 3 criteria confirm a substance as a neurotransmitter?
1. It is present in the presynaptic neuron (usually established by immunostaining for the presence of specific enzymes required for its synthesis). 2. It is released from the presynaptic terminal in response to membrane depolarization in Ca2+-dependent manner (usually difficult to establish for central synapses). 3. It binds to specific receptors on the postsynaptic cell (usually established in experiments with specific pharmacological agents acting on postsynaptic receptors).
Review: What are the 2 steps of the Recycling phase (less than 1 minute)?
1. Synaptic vesicles that underwent exocytosis are retrieved by endocytosis. 2. Retrieved synaptic vesicles are refilled with neurotransmitter and added to "reserve pool" of vesicles.
Review: What are the 9 steps of the Excitation-secretion coupling phase (less than 1 ms)?
1. The action potential propagates along the axon and invades the presynaptic terminal. 2. Presynaptic membrane depolarization opens presynaptic voltage-gated calcium channels. 3. Calcium channel opening allows rapid influx of calcium ions (Ca2+) into presynaptic terminals. 4. Synaptic vesicles (docked in the immediate proximity of calcium channels) are exposed to high Ca2+ concentration. 5. Ca2+ binding induces triggers vesicle fusion with the presynaptic membrane. 6. The content of synaptic vesicles (neurotransmitters [NT]) is released into synaptic cleft via exocytosis. 7. Neurotransmitter molecules diffuse across the synaptic cleft bind to postsynaptic receptors. 8. Ligand-gated channels (NT receptors) in the postsynaptic membrane open. 9. Postsynaptic current causes excitatory (EPSP) or inhibitory (IPSP) postsynaptic potentials that modify the excitability of the postsynaptic cell.
Review: What are the 4 steps of the Recovery phase (less than 1 second)?
1. The presynaptic membrane potential returns to the resting value. 2. Presynaptic calcium channels close following membrane hyperpolarization. 3. NT molecules are cleared from the synaptic cleft (by breakdown or reuptake). 4. Synaptic vesicles from the "reserve pool" are docked near presynaptic calcium channels.
What is the clinical importance of serotonin?
A rich pharmacology of 5-HT agonists and antagonists is used clinically. Several types of *antidepressants* enhance serontonergic transmission by blocking re-uptake (Prozac and others) or inhibiting enzymatic degradation (monamine oxidase inhibitors - MAOIs). Agonists are used to treat *migraine headache* (the "triptan" drugs, sumatriptan and others). Antagonists of the ionotropic 5-HT3 receptor alleviate *nausea / vomiting* and are used as pre-treatment in cancer chemotherapy.
How can Alzheimer's disease be treated in terms of Ach?
AChE inhibitors are also used to slow memory loss in the neurodegenerative disorder Alzheimer's disease where there is a deficiency in cholinergic projections.
What are the three different kinds of ionotropic receptors for glutamate?
AMPA, NMDA, Kainate (kainate grouped with AMPA)
Where are the dopaminergic neurons located? Loss or gain of function at each of these regions can cause what, respectively?
Activity of DA neurons at the base of the brain (substantia nigra projecting to the basal ganglia) is essential for the timing and initiation of movement. Degenerative loss of these DA neurons causes Parkinson disease. Conversely, excessive DA signaling produces involuntary movements. The ventral tegmental area in the brain stem is a source of dopaminergic neurons that project diffusely to cerebral cortex. These DA systems are important for modulating reward / addiction behaviors and excessive activation may produce psychosis with auditory and visual hallucinations.
Drugs that are used to treat what act through GABA receptors and potentiate inhibition?
All barbituates; sedatives, hypnotics, anti-spasticity analogs of GABA: anti-epileptics
Serotonin receptors are both ionotropic and metabotropic or only one?
Both - but majority are metabotropic - only one ionotropic, though it is important (target for drugs treating nausea)
Where are Ach muscarinic receptors found? Are they ionotropic or metabotropic?
Brain, heart, smooth muscle, salivary glands; metabotropic
Two important things to remember about NMDA receptors: They are permeable to one ion that AMPA/Kainate is not. Which is it? They are co-incidence detectors. What does this mean?
Co-incidence detection: A distinctive feature of the NMDA receptor is block of the pore by external Mg2+ (Fig 6 C,D). Because the Mg2+ binding site is within the transmembrane segment of the pore, the potency of block is greater at negative membrane potentials. (The negative membrane voltage at Vrest will electrostatically favor Mg2+ occupancy of the pore and therefore increased binding and block.) Depolarization expels Mg2+, relieves the block, and allows passage of ionic current. *Through this mechanism, NMDA receptors act as coincidence detectors*. Namely, the NMDA receptor allows Ca2+ entry only when both the receptor binds glutamate and the postsynaptic membrane is depolarized.
What kinds of things do intracellular signalling mechanisms do? Their defining characteristic is that they allow a signal to be __________.
DO NOT MEMORIZE THESE increase or decrease likelihood of phosphorylation; amplified - their action results in tremendous amplification and a great array of signalling opportunities made available
What is the biological pathway for serotonin? Most neurons releasing seratonin can be found where?
Dorsal part of the brain stem - raphe nuclei
Epinephrine is generated from NE by what? Where are epinephrine containing neurons found?
Epinephrine is generated from NE by phenylethanolamine-N-methyltransferase (PNMT). Epinephrine containing neurons are present in the rostral medulla; their function is not completely understood.
If the conductance becomes available because the channel opens, it's going to try to pull the membrane potential towards the _____ of that conductance.
Erev
Ach Nicotinic receptors are excitatory or inhibitory? Ionotropic or metabotropic? Non-selective or selective? Where can they be found?
Excitatory; Ionotropic; cation non-selective conductances; found at the NMJ, autonomic ganglia, brain
What is the major inhibitory neurotransmitter of the brain?
GABA
GABA ionotropic receptors (GABAaR) open what kind of channel? GABA Metabotropic receptors (GABAbR) are coupled to which kind of channel?
GABAA receptors are ionotropic ligand-gated Cl- channels that open rapidly and produce a transient IPSP lasting 5 - 20 msec in mature neurons where the K+/Cl- transporter is expressed and ECl is ~ -70 mV. Since ECl is approximately equal to Vrest the IPSP may be hyperpolarizing (ECl <Vrest), depolarizing (ECl >Vrest) or even have no detectable change in membrane potential ECl = Vrest. In all cases, however, ECl may be <Vthresh and so the response inhibits firing in the post-synaptic neuron. Stimulation of GABAergic interneurons causes a transient inhibition of action potential firing by activation of GABAA receptors. GABAB receptors are metabotropic receptors that are coupled to activation of K+-selective channels.Because EK < Vrest, a hyperpolarizing IPSP is observed with GABAB receptor activation. Typical of metabotropic receptors, the IPSP has a delayed onset and may have a prolonged duration of seconds to minutes. Also linked to CaV channels - inhibits them
What is the mechanism of action via which GABAbR decreases excitability of the cell?
GABAbR ligand binds -> Beta/Gamma dissociate from Beta/Gamma/Alpha -> associate with K+ channel -> open K+ channel -> decreases excitability of cell (thus inhibitory)
Glutamate: What is it synthesized from? Where must it be synthesized?
Glutamate DOES NOT cross the blood-brain barrier - must be synthesized in the pre-synaptic terminal from glutamine (illustrated above)
Typically, histamine is thought of as a hormone but it also acts as a NT in the CNS. What is it important for? In the CNS, histamine is produced from what and by which enzyme?
Histamine is produced from histidine by the enzyme histidine decarboxylase. Histamine acts as a hormone when released from mast cells; however, histamine acts as a neurotransmitter in the CNS. Histamine containing neurons are located in the hypothalamus (project out of the reticular activating system in the brain stem) and activity of these neurons facilitates the maintenance of the waking state (sleep-wake cycles).
If Erev is 0 when resting potential is negative, what does this say about whether the action is inhibitory or excitatory?
It is excitatory, because it is becoming depolarized. In an inhibitory action, Erev would be more negative than the resting potential (hyperpolarize).
Describe the experiment that demonstrated the "quantal theory of synaptic transmission."
In this experiment, a sensing electrode was placed in a muscle, there was no stimulation provided. The lines show activity of the muscle (there is no significance to the vertical ordering of the lines). MEPP = miniature end plate potentials In understanding the MEPPs, the timing was random but each amplitude is about the same - 0.4mV *These events were eliminated by curare (Ach receptor blocker), thereby proving these were caused by synaptic activity.* Experimenters realized that Ca was critical for an AP to occur, so they used very low Ca (so that synaptic potential was not swamped out by AP) and then added a stimulus. Again, distribution was not random. *EPP in this experiment was in integers of MEPPs! Ex: 0.4, 0.8, etc, providing support for the idea that synaptic vesicles were transmitted in quantal amts.* The graph on the bottom right shows that with normal calcium, the summation of all of the miniature events (MEPPS) into an excitatory post-synaptic potential would far exceed threshold. Gives a sense of the amplitude of the synchronized release compared to individual miniature events which are demonstrated in purple).
GABAbR affects another channel discussed in lecture. What is it? What affect does it have?
Inhibitory for Ca channel via interaction with Beta/Gamma units
Which drugs target GABAaR receptors specifically? These are Ionotropic or metabotropic?
Ionotropic
How many subunits does GABA have?
It is pentameric
Which drugs target GABAbR receptors specifically? These are Ionotropic or metabotropic?
Metabotropic
The fact that both Na+ and K+ influence Erev for the ionotropic channel at the end plate suggests that the channel is selective or non-selective?
NON-selective for monovalent cations (Chloride had no effect on Erev).
Peptide NT are much larger than small NTs. What are some of their important functions? In contrast to small NTs, where are they synthesized? Also in contrast to small NTs, how are they dealt with after release?
Neuropeptides modulate complex behaviors such as perception of pain (substance P, endorphin, enkephalin) or response to stress (endorphin). In comparison to small-molecule neurotransmitters, neuropeptide transmitters have some notable differences. Neuropeptides are synthesized and packaged in synaptic vesicles as pro-peptides in the cell body, transported into the terminal by axonal transport and converted to the active form in the terminal. This contrasts with small molecule neurotransmitters that are synthesized and packaged in the nerve terminal. After vesicle release into the synaptic cleft, peptide neurotransmitters are proteolytically degraded, whereas re-uptake transport systems are more common for small molecule neurotransmitters.
Norepinephrine is generated from dopamine by what? Where can NE neurons be found? What do they play a role in? What is a drug that stimulates their release?
Norepinephrine (NE) is generated from dopamine by dopamine-β -hydroxylase. NE neurons are largely restricted to a cluster of cells in the brain stem (locus coeruleus) and play a major role in the modulation of arousal states (wake and different sleep states). The stimulant drug amphetamine promotes release of NE.
Describe the following for both AMPA & NMDA: EPSC (excitatory post-synaptic potential), permeability (what ions can come through?), and function (what does it do?)?
Note: Kainate should be grouped with AMPA
How is a chemical synapse defined?
One that packages a NT in presynaptic vesicles that are released in quanta in response to Ca entry
What did competition for [Ca] release by Mg show? What clinical relevance does this have?
Open symbols show lowest Mg, filled circle shows highest Mg; as Mg increased, there was less and less amplitude of the post-synaptic response During pregnancy ocassionally in the 3rd trimester there is preeclampsia with hypertension, loss of protein via urine, and susceptibility to seizures. They are given IV Mg-sulfate - this Mg competes with Ca to reduce synaptic activity - try to prevent seizures.
What is an example of an irreversible inhibitor of AChE (acetylcholinesterase)?
Organophosphate poisons (nerve gas, such as sarin) are irreversible inhibitors of AChE.
Synthesis of GABA begins with what? What is the enzyme that catalyzes its production (rate-limiting enzyme)? It works with a cofactor, what is this cofactor?
Precursors for GABA synthesis include glucose, pyruvate or glutamine. The final step is catalyzed by glutamic acid decarboxylase (GAD) for the conversion of glutamate to GABA. GAD requires a co-factor derived from vitamin B6(pyridoxal phosphate) and deficiency can lead to impaired GABA synthesis and seizures.
Wanna see a pretty picture?
Rat hippocampus soma and dendrites are orange axons are yellow
Describe the sequence of events that follow ligand binding to an ionotropic receptor.
Receptor binding induces a rapid (~1 msec) increase in channel opening, thereby producing an increase in conductance, G. The postsynaptic current will be determined by the "driving force" of V - Erev. If V - Erev < 0 (i.e. V < Erev) then the current is inward (depolarizing). Finally, the postsynaptic current produces the PSP (postsynaptic potential). Recall, the PSP will be determined by the postsynaptic current acting on the RC properties of the postsynaptic membrane. The membrane capacitance slows the voltage change and therefore the time to peak and duration of the PSP are longer than for the postsynaptic current transient.
What is a clinical implication concerning epilepsy of the excitability of GABAaR?
Some epileptic patients are given a drug that stimulates GABAaR in order to inhibit excitability. However, if because of the biology of the seizure the intracellular Cl has changed, GABAaR may now have become excitable and are no longer inhibitory. The drug will then have deleterious effects.
What proteins are involved in docking synaptic vesicles to the presynaptic plasma membrane? Which one specifically acts as a Ca sensor to initiate docking? *Must know this slide*
Synaptobrevin & Syntaxin - two integral membrane proteins with long alpha helical extensions SNAP-25 - cytosolic protein These all come together to dock the synaptic vesicle Synaptotagmin - membrane spanning protein with characteristic negative charges which is a binding site for Ca. Once Ca is there it triggers conformational changes that favor fusion and exocytosis of material. Hint for remembering: Both proteins that begin with "synapto" are located in the synaptic vesicle membrane
What two substances combine to make acetylcholine? What enzyme catalyzes this reaction? What enzyme is used to stain for nerve terminals to see if they are cholinergic? How is removal of Ach in the synaptic cleft achieved? Via what kind of transporter is choline brought back into the end terminal?
Synthesis occurs in the cholinergic nerve terminals from precursors acetyl Co-A and choline, whose conversion to ACh is catalyzed by choline acetyltransferase (CAT - this is the rate-limiting enzyme and is used to stain for nerve terminals to see if they are cholinergic). Unique to cholinergic synapses, removal of neurotransmitter is not by re-uptake but rather is performed by rapid hydrolysis with acetylcholine esterase (AChE), followed by a uptake of choline to be recycled. Note: VAchT = Vesicular Ach Transporter
T/F: A synaptic event will always lead to an AP in the post-synaptic cell.
TRUE for motor neurons, but FALSE overall because for many synapses in the CNS a single synaptic event does not always illicit an AP in the post-synaptic cell.
What is Lambert-Eaton myasthenic syndrome caused by?
The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder caused by antibodies against the voltage-gated Ca2+ channel. Presynaptic Ca2+ entry is impaired and the safety factor of neuromuscular transmission is reduced, which causes fatigue and weakness.
In measuring End Plate Current, what would you expect to see when the voltage of the membrane is very negative, around -100mV? What about when it is less negative, around -60mV? When it is positive, +70mV? What do we expect when the voltage is 0mV? What is unique about this voltage?
The amplitude and direction of the EPC depend on the voltage of the postsynaptic muscle fiber. At more negative potentials a large inward current is produced by the influx of Na+ ions. At positive voltages the synaptic current is outward (positive) due to the efflux of K+ ions. At an intermediate voltage (~ 0 mV) the net current flow is zero because the influx of Na+ and efflux of K+ are balanced. Recall that the voltage at which the current = 0 is the reversal potential (Erev) because the net current reverses direction from inward to outward (Fig. 6. Top, right panel) as the voltage is varied < Erev (inward) to > Erev. (outward).
Compare the chemical synapse with the electrical synapse in relation to the following terms: abundance in body, continuity with other cells, direction of signalling, threshold levels, delay (latency). What three features of electrical synapses lead to synchronized activity for clusters of neurons?
The following attributes synchronize activity for clusters of neurons: Reciprocal pathway ( pre ↔ post) for electrical current and small organic molecules Fast signaling (< 1 msec) with no delay Subthreshold events are communicated between cells
What experiment showed that Ca is SUFFICIENT for a postsynaptic event?
The graph on the left shows Ca injection into the cell - so when Ca blocked, and when Ca injected, you CAN get a postsynaptic response Ca was buffered pre-synaptically (meaning it was already in the pre-synaptic terminal), and it was shown that no post-synaptic event occurred when Ca was buffered. *This showed that Ca is SUFFICIENT to produce a post-synaptic event* - there is nothing else that is needed to cause the postsynaptic event
What experiment showed that neurotransmitter quanta corresponded to the exocytosis of the contents from one synaptic vesicle?
The presynaptic face of the synaptic cleft was accessed by rapid freeze-fracture and imaged by electron microscopy. Rows of intramembranous particles are Ca channels. Ultrafast flash freezing after nerve stimulation revealed "pits" created by exocytosis of vesicles. The number of "pits" and the size of EPP increased as the duration of the action potential was increased pharmacologically using the Kchannel blocker 4-AP (illustrated in the graph). *These data support the notion that NT quanta correspond to the exocytosis of the contents from one synaptic vesicle.*
If Erev is defined by both permeability to ions and the concentration gradient of those permeant ions, what will happen to Erev in the following two situations (Hint: think about the equation for Nernst potential): Na+ outside is decreased K+ outside is increased
The reversal potential for the EPC is 0 mV and not equal to EK or ENa because the nAChR is very permeable to both ions. If the concentration gradients for Na+ or K+ were to change, then Erev should shift. Lowering extracellular [Na+] would shift Erev more negative where as increasing extracellular [K+] would shift Erev more positive
Where are synaptic vesicles in relation to Ca channels? Why is this important?
The synaptic vesicles must be docked and ready to go - since they are signaled via calcium, the calcium must be just adjacent to the vesicles in order to keep signaling potent and localized.
T/F: Glutamate is important in learning & memory processes
True - "synaptic plasticity" - Nearly half of all synapses in the brain are glutamatergic and modulation of synaptic strength (amplitude of EPSP) at glutamatergic synapses is a fundamental mechanism for learning and memory
T/F: A neurotransmitter may use more than one class of receptor (metabotropic vs ionotropic).
True - A neurotransmitter may use more than one class of receptor at different locations in the nervous system. For example, acetylcholine acts on nicotinic AChRs at the NMJ, whereas acetylcholine activates muscarinic receptors (and other nicotine types) in the brain.
T/F: The reversal potential of ionotropic receptors determines whether synaptic transmission is excitatory or inhibitory.
True - along with threshold and where the two are in relationship to each other
T/F: There can be axo-axonal synapses.
True.
T/F: There can be synapses directly on the soma.
True.
What experiment showed that depolarization causes Ca release? What modification of this experiment showed that Ca is NECESSARY to have synaptic transmission?
Used voltage clamp, depolarized the terminal, and measured Ca current *This demonstrated that Ca was released in response to depolarization* depolarized membrane to same amount, used Ca blocker (prevented Ca from entering the pre-synaptic terminal) - demonstrated that no post-synaptic event ocurred when Ca blocked *This specifically showed that Ca is NECESSARY to have synaptic transmission* - no Ca, no postsynaptic event
How is odor transduction communicated via the G-GTP receptor?
Uses cAMP These are used in the senses for two reasons: 1) High sensitivity is needed 2) Also want to be able to adjust the gain
What packages GABA into the pre-synaptic terminals? Termination of response is mediated by what? What cell uptakes GABA? What kind of transporter facilitates uptake?
Vesicular inhibitory amino acid transporter; Released GABA is cleared from the synaptic cleft by uptake transporters (GAT) on both presynaptic terminals and glia.
Must a threshold be met in order for a synapse to occur?
When electrical synapses are present, the latency is much much shorter than in a chemical synapse - even subtreshold events can be communicated - do NOT need to exceed treshold.
There is great ________ of signal with metabotropic receptors, while ionotropic receptor response is......? Which one takes longer to transmit the signal?
amplification; one to one; metabotropic takes longer
Biogenic amines describe which NTs?
catecholamines (epinephrine, norepinephrine, dopamine) as well as serotonin
What are connexons?
connexons are the actual pores that make up the gap junction channels
About how many neurons are there in the brain? About how many synapses?
each neuron has about 1,000 synapses
Loss of function mutations in glycine receptors can cause what? What poison targets glycine?
excessive excitation of motor neurons in the spinal cord and increase startle response and spasticity; strychnine poisoning
Early in development, GABAaR is excitatory or inhibitory? Later in development it is excitatory or inhibitory? Why is this?
excitatory; inhibitory Early in development intracellular [Cl-] is high, making ECl relatively depolarized (~ 0 mV - Recall: ("flip" ratio for anions) ratio of in to out approaches 1 and log of this is 0) and so application of GABA produces excitation (EPSP). In mature neurons a different Cl- transporter is expressed, which sets internal [Cl-] low, makes ECl negative (-60 mV) causes inhibition (IPSP) by activation of the GABAAR
What defines the electrical synapse?
gap junction channels through which ions pass
What experiment demonstrated synaptic vesicle recycling?
horseradish peroxidase (HRP) is just a marker used to show up in electronmicrographs Presynaptic terminal stimulated to illicit exocytosis event to create need for endocytosis. A few minutes after stimulation, began to see HRP in endosomes. Then the endosome is recycled and is the source for providing the synaptic vesicles themselves. AP invading and release of synaptic vesicle is around 1 ms; "recovery phase" occurs in less than 1 second (membrane back to resting value, NT cleared from cleft, new synaptic vesicles docked, etc); takes around a minute for membrane to be recycled - synaptic vesicles filled with NT and redocked
Glycine is a major inhibitory NT in the _______ and _______. What kind of receptors does it act on? What channel do these affect?
ionotropic - Cl- channels
The GABAa receptor (GABAaR) is what kind of receptor? It has how many subunits? It activates what kind of channel?
ionotropic; pentameric; chloride selective channel (Erev determined by chloride)
What are the two types of neurotransmitter receptors?
ligand binds to receptor molecule, and that causes the opening (usually) in that very same molecular complex - combination channel & receptor Metabotropic receptor - involved in signal cascade events - often times signal is an electrical event - but connection between ligand binding and the ocurrence of an electrical event has intervening steps
Describe what can be found at the synaptic terminal. Where can synaptic connections occur besides between axons and dendrites? What is found on the postsynaptic cell?
mitochondria - this is a metabolically active part of the neuron - need localized source of energy The synapse is a highly specialized structure located at the place of contact between a presynaptic and a postsynaptic cell. Synaptic connections are most commonly located at contacts between the axon terminal and dendrite, but may also be where the axon contacts the soma or even another axon. Chemical synapses consist of presynaptic terminals filled with synaptic vesicles that contain neurotransmitter (NT), a narrow synaptic cleft that separates the pre- and postsynaptic cell and a postsynaptic density in the postsynaptic cell that contains large numbers of postsynaptic receptors. The propagation of information from the presynaptic to the postsynaptic cell is defined assynaptic transmission.
What are the two groups of ionotropic receptors (as defined by structure)? Which group makes up the minority?
pentameric (majority) & tetrameric (glutamate receptors) tetrameric - group of GLUTAMATE receptors that are excitatory in the brain
What toxin prevents docking of the synaptic vesicle to the presynaptic plasma membrane?
toxin is taken up by motor presynaptic terminals and it cleaves the proteins involved in docking of vesicles - efficacy of neuromuscular junction is compromised
Catecholamine synthesis begins with what molecule? What is the pathway? Generation of what is the rate-limiting step in the biosynthesis pathway?
tyrosine; generation of DOPA is the rate-limiting step