Neurons And Synapses + Muscles Flashcards
What are the two kind of synapses?
Electrical and chemical synapses
What is the synapse?
It is the connection between two cells; it can be considered a junction only in the cases of electrical synapses
Describe electrical and chemical synapses
- ELECTRICAL: The pre-synaptic and post-synaptic terminal are very close and the synaptic cleft is very narrow; the two terminals communicate through Gap junctions which allow for ELECTRICAL CONTINUITY and flow of ions; it is very fast. The two synapses are structurally and functionally very similar and the flow of ions can be bidirectional.
- CHEMICAL: The pre-synaptic and post-synaptic terminal leaver a bigger gap between them, so we have a wider synaptic cleft; the pre-synaptic terminal releases neurotransmitters that bind to receptors on the post-synaptic membrane, opening channels and allowing the depolarization. It is slower compared to electrical synapses and the two synapses are structurally and functionally different; the flow of current is unidirectional.
Definition of a NEUROTRANSMITTER
- Must be produced by the neuron
- It needs to be released by the neuron upon stimulation
- The effect on the post-synaptic cell should be the same if you release it directly from the neuron or if you add it exogenously
- The effect of pre-synaptic stimulation should be able to be modified in the same way by different substances
TRUE OR FALSE
- The neurotransmitter is an agonist
- The drugs targeting neurotransmitter receptors can be considered both agonists and neurotransmitters themselves
- T
- F
How can we classify neurotransmitters?
- SMALL molecule neurotrasmitters
- BIG molecule neurotransmitters
What is the difference between big and small molecule neurotransmitters?
- SMALL MOLECULE NEUROTRANSMITTERS: Are synthesised locally in the presynaptic terminal, after the enzyme for it is produced in the cell body; after exocytosis the precursor molecule is uptaken by the synapse to be reused
- BIG MOLECULE NEUROTRANSMITTERS: Both the enzyme and precursor are produced by the cell body and then synthesised in the terminal; after exocytosis the molecule is degraded completely.
Describe the chemical transmission process
The neurotransmitter is packed into vesicles and anchored to the presynaptic internal side of the membrane; the action potential depolarizes the synapses causing the opening of Calcium voltage-gated channels, causing an inflow of calcium that will result in the fusion of vesicles with the membrane and release of neurotransmitter in the synaptic cleft. Then there is the activation of post-synaptic receptors and channels, and postsynaptic potential; then the neurotransmitter is removed by the cleft either through degradation or diffusion.
What are ACTIVE AREAS?
Specialized areas of the presynaptic membrane where exocytosis happens thanks to Ca2+ dependent processes
What are V-SNAREs and T-SNAREs proteins?
-V-SNAREs are proteins located on the vesicles membrane, like SYNAPTOBREVIN; these interact with T-SNAREs proteins, found on the terminal’s membrane, like SNAP-25 and SYNTAXIN-1, which are essential for the fusion process.
TRUE or FALSE
- The amount of neurotransmitter released is proportional to the Firing Frequency of the presynaptic neuron.
- The postsynaptic potentials are graded potentials which propagate electrotonically.
- The postsynaptic current can be inhibitory or excitatory based on the flow of ions activated by the neurotransmitters.
- T
- T
- T
What is the TRIPARTITE SYNAPSE?
It is a conformation of synapse where there is the participation not only of neurons but of astrocytes/glia cells too.
It is very useful in the case of glutaminergic synapses: the neurons release glutamate, the most important neurotransmitter in our brain, but cannot take it back; it is therefore taken up by the astrocytes which convert it back to the precursor, glutamine, and released so that the neuron can pick it up and use it again.
What is a QUANTAL RELEASE?
It is the minimum release of a neurotransmitter, equivalent to one vesicle content: NEUROTRANSMITTER QUANTUM.
These are sufficient to induce a miniature synaptic potential.
What are TEMPORAL and SPATIAL SUMMATION?
-TEMPORAL SUMMATION: One single presynaptic neuron fires multiple potentials, which if close enough in time can be summed up and could cause action potential in post-synaptic cell; depends on FIRING FREQUENCY.
-SPATIAL SUMMATION: Multiple presynaptic neurons send their input almost simultaneously, leading to summation and possibly to action potential.
These two kinds of summation can coexist.
-The threshold doesn’t depend on a single input, but on all the dendrites on that neuron.
What is the CABLE THEORY for dendrites?
-Cells receive both inhibitory and excitatory inputs, what makes the difference is the firing frequency of the presynaptic neuron; this is what will decide whether the neuron will hyperpolarize or depolarise.
What is the difference between agonists and antagonists?
- AGONISTS mimick the action of the neurotransmitter
- ANTAGONISTS block the action of neurotransmitter
What are the two general categories of neurotransmitter receptors?
- IONOTROPIC: The receptor is itself the channel, therefore the binding of the neurotransmitter directly opens the channel; the faster way.
- METABOTROPIC: The receptor is not a channel, but the binding with the neurotransmitter will open channels through the action of secondary messengers; the slower way.
Describe ACETYLCHOLINE
Acetylcholine is a small molecule neurotransmitter, synthsiozed by the fusion of choline with Acetyl-coA, an enzyme coming from metabolic production; after exocytosis it is degraded by acetylcholinesterase and the choline is taken back up into the neuron. It is the only neurotransmitter which has only degradation as a removing-from-cleft mechanism.
It has both ionotropic and metabotropic receptors, called NICOTINIC and MUSCARINIC receptors
What are CATECHOLAMINES or BIOGENIC AMINES?
A family of neurotransmitter with mainly mood and behaviour related functions, which includes DOPAMINE, ADRENALINE AND NORADRENALINE.
They only have METABOTROPIC RECEPTORS.
TRUE or FALSE
- Dopamine, Noradrenaline and Adrenaline have all a common biosynthetic pathway starting from TYROSINE.
- Synaptic transmission is terminated only through degradation in the cleft by MOA.
- They all originate in the same part of the brain
- Every synapse releasing biogenic amines is able to release all of them together.
- T
- F
- F
- F
Origin and function of DOPAMINE
Dopamine originates in the SUBSTANTIA NIGRA and VENTRAL TEGMENTAL AREA; it is responsible for motivation, reward and reinforcement, it also works as a PARACRINE hormon.
Origin and function of NORADRENALINE
Noradrenaline originates in the LOCUS COERULEUS and it is the main neurotransmitter of the SYMPATHETIC NERVOUS SYSTEM; responsible for fight-or-flight response.
Origin and function of ADRENALINE
Adrenaline originates in the MEDULLA and has a similar function to noradrenaline, being involved in the sympathetic system and fight-or-flight response.
Origin and function of SEROTONIN
Serotonin originates in the RAPHE or the brain and it is involved in many cognitive functions and sleep-wake rhythm.
Describe GLUTAMATE
The only purely excitatory neurotransmitter and the main neurotransmitter of the brain; it is synthesised by Glutamine through glutaminase found in neurons. After exocytosis it is taken up by glia cells which convert it back to the precursor glutamine in order to be picked by by neurons again.
Excess glutamate cause accumulation of Calcium inside of the cell, which is highly toxic and leads to cell death: EXCITOTOXIC effect.
Describe GABA
GABA is the main inhibitory neurotransmitter of the brain; its release activates the opening of chlorine channels, allowing an inflow of the ions in the cell and its hyperpolarization.
GABA is essential for maintaining the balance in the brain, keeping excitation at a minimum.
In the first stage of development, in foetus’ brain, it has an EXCITATORY function, due to the fact that the extracellular fluid is less rich in chlorine compared to the inside of the cell, therefore the opening of channels causes a depolarization of the cell.
Describe GLYCINE
GLYCINE is an inhibitory neurotransmitter, and has a very similar function to GABA, also opening Chlorine channels. The difference is that glycine is mainly found in the spinal cord where there are motor neurons.
Why would we rather use even metabotropic receptors rather than all ionotropic receptors, given that the latter are faster?
If we want to activate also other pathways and the potential has to mediate other things, rather than simply depolarise the cell, we need to use metabotropic receptors; that is why we often have both.
Describe the G PROTEIN COMPLEX
The G PROTEIN COMPLEX is found in metabotropic receptors; it has 7 transmembrane domains which form a single subunit. We also find an alfa-subunit, a beta-subunit and a gamma-subunit. The alfa-subunit is the main subunit; it will use the energy obtained by hydrolysing GTP to activate different effectors, which could be intracellular messengers or directly channels.
The other two subunits form together the beta-gamma complex, which is also able to activate channels.
What are the kinds of GLUTAMATE receptors?
We have three ionotropic kind of receptors:
-AMPA receptors, mainly permeable to sodium and potassium
-NMDA receptors, permeable to sodium, potassium and high permeability for calcium
-KAINATE receptors,very generic cationic channels
We also have three groups of metabotropic receptors.
Why are NMDA receptors so important?
They are usually blocked by voltage-dependent magnesium blocks; with a higher depolarization compared to AMPA channels they open allowing calcium to flow in and the release of even more glutamate.
This process is very important for synaptic plasticity and to control the flow of calcium in the cell which can be toxic.
TRUE or FALSE
- Acetylcholine has both ionotropic and metabotropic receptors
- Only ionotropic channels are composed of 5 subunits
- Acetylcholine receptors have at least 2 binding sites
- The metabotropic receptors activate sodium channels
- The adult ones have a gamma subunit, while the embryo have an epsilon subunit
- Muscarinic receptors can be both excitatory (M1,M3,M5) and inhibitory (M2, M4)
- T
- F. Even metabotropic receptors are made up of 5 subunits
- T
- F. They activate potassium channels
- F. The opposite
- T
What is Cis-loop superfamily of receptors?
A superfamily of ionotropic receptors, which includes Acetylcholine, GABA, Glycine and Serotonin receptors.
The cis-loop is the characteristic disulphide bond on the extracellular part of the subunits; it is made up of 5 subunits.
Why do we say the neuromuscular junction is a very efficient synapse?
Because:
- We have a lot of synaptic vesicles, each containing more than enough acetylcholine to saturate nicotinic receptors
- For each action potential only a few of the vesicles can be released, depolarizing at least +40 mV
- For each action potential in the neuron will follow an action potential in the muscle too.
TRUE or FALSE
- The post-synaptic potential in neuromuscular junctions is called END PLATE POTENTIAL
- The end plate potentials are electrotonical potentials
- The rising of current in endplate potential is biphasic
- We only need one acetylcholine molecule to fully activate the receptors and cause a depolarization
- T
- T
- T
- F
Why do we have a delay in the end plate response?
It is the time needed for the release of ACh, its diffusion in the synapse and the opening time of the postsynaptic acetylcholine receptors
What are miniature end plate potentials?
They are miniature potentials created by the spontaneous leak of acetylcholine in the cleft, even in the absence of action potential; these measure about 0.4 mV, which is equivalent to one acetylcholine-containing vesicle.
Give definition of CONFORMATION TIME and PRIMED STATE, in relation to neuromuscular synaptic transmission
- CONFORMATION TIME: The time the channels need to pass from closed to open state
- PRIMED STATE: A state where channels are still closed, but more ready to open
TRUE or FALSE
- Increasing the concentration of acetylcholine released will cause longer opening state in the channels of the receptors
- One single acetylcholine vesicle is able to activate more than one receptor
- T
- T
- Alpha-bungarotoxin A. ACh blocker
- Nerve gases B. ACh ir. agonist
- Botulinum toxins/tetanus C. Vesicles release
- Tubocurarine D. ACh i. a-agonist
- Alpha-latrotoxin E. AChE inhibitors
- 1.B
- 2.E
- 3.A
- 4.D
- 5.C
TRUE or FALSE
- Axons and neurons cannot ever regenerate, neither in the CNS nor PNS
- In the CNS, the exception are the olfactory bulb and dentate gyrus neurons
- EFFERENT outputs move from CNS to the periphery, while AFFERENT inputs move from the periphery to the CNS
- F
- T
- T
Describe GLIA CELLS
They are family of cells defined partly by what they lack: axons, action and synaptic potentials. In the CNS we can find different kind of glia cells such as ASTROCYTES, OLIGODENDROCYTES, MICROGLIA cells, stem cells and ependymal cells. In the PNS we can find SATELLITES cells and SCHWANN CELLS.
What is the role of astrocytes in neuron metabolism?
The neurons have to ways to produce ATP to sustain their metabolic functions: a direct way and an indirect way; the astrocytes, being connected to both neurons and blood vessels are involved in the indirect pathway. With the direct pathway, from one molecule of glucose, the neuron can obtain 30 molecules of ATP through oxidation.
Through the indirect pathway, the astrocytes pick up extra glucose and convert it into lactic acid, which is broken down passing through the neuron in 28 molecules of ATP.
What is the function of oligodendrocytes in CNS and Schwann cells in PNS?
They produce and maintain the myelin around the myelinated axons; oligodendrocytes cannot regenerate myelin if damaged, unlike Schwann cells.
They have two different mechanisms to form the myelin:
-Oligodendrocytes use their processes to form the myelin, not their body.
-Schwann cells wrap their cell body around the axons and stay like that even after the production of myelin is complete.
TRUE or FALSE
- Microglia can produce both inflammatory and anti-inflammatory cytokines.
- The brain ph is weakly basic
- Astrocytes have a higher permeability to potassium compared to neuronal membranes
- T
- F. It is weakly acid
- T
What are the two kinds of plasticity associated with long-term memory storage?
- SHORT-TERM PLASTICITY: usually only affects the presynaptic terminal and last a few minutes, enough to store a memory
- LONG-TERM PLASTICITY: affects both the presynaptic and postsynaptic terminal and is usually followed by a change in conformation of dendritic spines.
Talk about short term plasticity
R is the ratio between the peak of the second post-synaptic response to the peak of the first one; if R=1 there is no plasticity. If R>1, therefore the first is smaller than the second response, then we have synaptic FACILITATION; if we have R<1, therefore the first is greater than the second response, then we have synaptic DEPRESSION.
Synaptic facilitation happens because after the first respinse there is still calcium in the presynaptic cell, which will result in a higher release of neurotransmitter in the cleft during the second potential.
In synaptic depression, the transmission is fast but the cell does not have enough neurotransmitter to release because of slow reuptake by transporters, or because of inactivation of presynaptic calcium channels.
What is the difference in the process for the activation of LONG TERM POTENTIATION and LONG TERM DEPRESSION?
The only difference is the amount of calcium that goes in the cell due to the firing frequency, high for LTP and low for LTD.
What are the characteristics of different muscle types?
- SKELETAL MUSCLE: Striated, multinucleated, nuclei sit at the sides of fibers, each individual cell is controlled directly by a motor neuron; it is a SYNCYTIUM, controlled by CNS.
- CARDIAC MUSCLE: Striated, multinucleated, nuclei sit in the center of fibers; connected by intercalated disks and gap junctions; functional syncytium, controlled by ANS.
- SMOOTH MUSCLE: Non-striate, mononucleated, connected by gap junctions; controlled by ANS; No neuromuscular junctions, varicosities along axons release neurotransmitters for stimuli.
What is the organisation hierarchy for epimysium, endomysium and perimysium?
Endomysium is connective tissue that wraps around the single muscle fibers made up by myofibrils; perimysium wraps around bundles of fibers; epimysium wraps around bundles of fascicles.
How is depolarization spread from the surface of the sarcolemma to the inside of the cell?
Through folds in the sarcolemma, called transverse tubules or T tubules, with together with the terminal cisternae of sarcoplasmic reticulum form the TRIAD and spread the depolarisation.
Describe the sarcomere
The sarcomere is the functional unit of the muscle; it is made up of contractile elements such as actin and myosin, supporting proteins like for example titin and nebulin, and regulatory elements like troponin and tropomyosin. It is bordered between two Z lines, which each divide the I Bands, containing only actin, in halves; then between the I bands there is the A band, composed by a mix of actin and myosin, and at the center of the a band we find the area H with only myosin and the M line, to which are anchored the myosin filaments.
What is Tropomyosin? And Troponin?
Both regulatory elements are found in the thin filaments of actin:
- TROPOMYOSIN is a dimer that wraps around the actin helix to avoid unnecessary myosin interactions.
- TROPONIN is a heterotrimeric complex formed by TROPONIN C, T and I, which in the absence of calcium inhibits the actin-myosin interaction. Troponin C binds to calcium and in case kicks the other two out of the way to allow myosin binding; Troponin T binds to tropomyosin and blocks actin; Troponin I binds to actin and inhibits the contraction, until Troponin C is activated.
MATCH TO FUNCTION
- NEBULIN. A.Binds actin to Z lines
- DYSTROPHIN. B.Elastic of the sarcomere, M to Z
- MYOMESIN. C.Binds myosin to M line
- TITIN. D.Mantain parallel orentation of fibers
- A-ACTININ. E. Binds sarcomere to sarcolemma
1-D 2-E 3-C 4-B 5-A
What is the SLIDING FILAMENT THEORY?
It is the theory that muscle contraction and shortening of sarcomere occurs thanks to the sliding of thick and thin filaments on each other. The myosin head slides over the thin filaments forming transverse bridges. Bands I shorten while band A remains unchanged; this is because of overlapping.
How does the cross-bridge cycle work?
It is a Calcium and ATP dependent process, for each cycle we need 1 ATP molecule.
- First the ATP binds to the myosin head, reducing its affinity for actin and causing the its release
- Then there is the ATP hydrolysis, the P remains bound to the myosin and cause it to stay in the cocked head state while it slides across the actin.
- The third state is a formation of a weak cross-bridge between actin and myosin
- Then the P is released which forms a strong cross-bridge state
- A conformational change in the head of the myosin allows the POWER STROKE
- Then the ADP is released and the myosin returns to the initial state of attachment.
How is the calcium released in the muscle cell in response to depolarisation?
The depolarisation moves from the sarcolemma surface along the T tubules and reaches the TRIAD, so in connection to the SARCOPLASMIC reticulum.
Then there is the opening of tetrameric voltage-gated calcium channels, L-type channels, on the membrane of T tubules, which mechanically opens tetrameric Calcium release channels on the SR terminal cisternae, allowing the flow of calcium into the cell and the activation of Troponin C and contraction.
TRUE or FALSE
- The SR Calcium release channels are also called RYRs because of the alkaloid plant Ryanodine which excites their action.
- Caffeine, another alkaloid plant, increases RYRs opening probability.
- F. Ryanodine inhibits the RYRs
- T
Why don’t we use PMCA (Plasma Membrane Calcium ATPase pump) for the removing of calcium from the cell after contraction, and instead prefer SERCA (Sarcoplasmic and Endoplasmic Reticulum Calcium ATPase pump)?
Because using PMCA to get rid of calcium, pushing it out of the cell, would eventually lead to depletion and shortage of calcium in the cell; while with SERCA, calcium is safely stored inside the Sarcoplasmic reticulum ready to be reused in the next cycle.
What is the difference between isotonic and isometric contraction in muscles?
-ISOMETRIC contraction happens when the load is too heavy compared to the tension produced by the muscle, therefore tension is produced but without the shortening of the muscle.
-ISOTONIC contraction happens when the tension is higher than the load and therefore we have both a force produced and the shortening of the muscle because of contraction.
We can also have ISOTONIC ECCENTRIC reactions when the load is heavier than tension therefore the muscle passively lengthens.
How is it possible to produce force without the shortening of muscle?
Based on Hill’s model, to shorten the tension produced by the muscle must be higher than the elastic tension of titin; therefore if that is not the case the muscle doesn’t shorten but the tendons are pulled and lengthen.
What is L0?
The optimal resting length, which is the length of the muscle where maximum active force develops after electrical stimulation.
At lengths lower than 60% of L0 there is no tension whatsoever. At lengths higher than 175 % we have no ACTIVE tension.
What are the determinants of muscle tension at the level of single muscle fibers?
- DIAMETER of fibers: The larger the diameter the stronger the force it will produce; that’s why we have myofibrils arranged in parallel, because you can add up the strength, which is not possible in series.
- LENGHT of sarcomere: At optimal length of the sarcomere we can produce the greatest tension.
- Cytoplasmic CONCENTRATION of Ca2+
- Frequency of stimulation
- MYOSIN ISOFORMS
What is an INCOMPLETE TETANUS and a TETANUS?
- INCOMPLETE TETANUS: The firing frequency of action potentials is high enough to add up, but not enough to produce a single contraction which has the same tension of all the others added up; so we will still have periods of relaxation.
- COMPLETE TETANUS: The firing frequency is higher so the interval of time is lower and we have a single contraction which is the sum of all the others. It is the physiological condition where the muscle produces maximum force.
TRUE or FALSE
- All isotonic contractions start out as isometric before turning into isotonic ones.
- The force needed to lift a load is directly proportional to the speed of contraction.
- In isotonic contraction there is delay between the increasing of tension and the shrinking of muscle.
- T
- F
- T
What are the isoforms of myosin?
Type I, Type IIa and Type IIb
What are the determinants of muscle velocity?
- Muscle ARCHITECTURE: Fusiform muscles are long and faster than Pennate muscles which by contrast are slower but stronger.
- Applied LOAD: heavier weight to lift means slower velocity of contraction compared to lighter weight.
- Types of MYOSIN.
What are the three metabolic pathways to produce ATP in muscle cells?
- AEROBIC OXIDATION: Needs oxygen, is the slowest but produces the most ATP, 36 molecules ATP/cycle
- ANAEROBIC GLYCOLYSIS: Doesn’t need oxygen, faster than oxidative phosphorylation, produces 2 molecules ATP from a molecule of glucose
- PHOSPHOCREATINE DEPHOSPHORYLATION : The fastest, produces 1 molecule of ATP/cycle by hydrolysing phosphocreatine and having the phosphate to bind to ADP.
What are the main functions of ATP in the muscle cells?
- Na+/K+ ATPase pump: to maintain the membrane potential and for diffusion of action potential.
- SERCA pump: for the uptake of calcium after contraction.
- POWER STROKE during cross-bridge cycle.
- CROSS-BRIDGE CYCLE START through binding to myosin.
What is muscle fatigue?
Muscles are unable to undergo a constant contraction for a continuous period, eventually they end up reducing the tension they produce, that is what we define as muscle fatigue.
On which factors does muscle fatigue depends?
- Ability to maintain energy, which depends on the metabolic pathway used.
- How many fibers are found in the muscle.
- What kind of fibers are present.
- Intensity and duration of stimulation, as longer and more intense stimuli will cause more fatigue.
Describe different kinds of muscle fibers and their characteristics
- SKELETAL SLOW (TYPE I) muscle fibers: Are very slow in their ability to contract, have a small diameter and generate very little force; they have a high oxidative capability, therefore have a lot of mitochondria, and high resistance to muscle fatigue; they are high in myoglobin which gives them a red color.
- FAST-OXIDATIVE (TYPE IIA) muscle fibers: Are fast to contract, have medium diameter and generate moderate force; they have a high oxidative capability but also work with glycolytic pathways, they have a moderate resistance to fatigue; they are high in myoglobin which gives them a red color.
- FAST-FATIGABLE (TYPE IIB) muscle fibers: Are fast to contract, have large diameter and generate high force; they get energy through glycolytic pathways and phosphocreatine dephosphorylation, therefore have very little resistance to fatigue; they are low in myoglobin and defined therefore, white fibers.
What are the determinants of muscle tension at the level of the entire muscle?
- Number, dimension and type of motor units.
- Frequency of stimulation of motor units.
- Percentage of different types of motor units.
- Architecture and length of the muscle.
TRUE or FALSE
- The motor unit is the connection between the motor neuron and all the motor fibers it innervates.
- A single motor unit can be made up of different kinds of muscle fibers.
- Small motor units are for precise movements, big motor units are for gross movements.
- The Slow Oxidative fibers are small motor units, the Fast Oxidative are medium motor units, the Fast Fatigable are large motor units.
- The order of recruitment is by size, from Fast Fatigable to Slow, and is the same are the order of un-recruitment, by Henneman’s Principle.
- T
- F
- T
- T
- F
