Neurobiology Flashcards
The Hoffmann reflex (H-reflex) results from direct electrical activation of which of the following types of sensory fibers?
A. II with non-spindle endings
B. III
C. IV
D. α
E. 1a
1a
The Hoffmann reflex, or H-reflex, was described by stimulating type Ia afferent sensory fibers at various intensities. At low intensity, the type Ia fibers result in a monosynaptic reflex arc with the efferent α motor, which results in activation of a motor unit recorded as an H-reflex. At higher intensities, there is direct activation of the α motor neuron terminus and motor unit (M-wave) which precedes the H-reflex wave that arises from orthodromic propagation. At even higher stimulus intensities, an antidromic wave through the motor neuron results in cancellation of the orthodromic H-reflex wave; and accordingly, only a large M-wave is detected. Non-contractile muscle spindle fibers are innervated by Ia sensory afferents conveying information of stretch and velocity, which excite efferent α motor neurons in the ventral horn. Type III and IV classes are slower conducting fibers that convey information of pain, temperature and chemical stimuli. Type II fibers with non- spindle endings are sensitive to deep pressure.
Excitotoxicity from prolonged activation of the NMDA receptor is caused by which of the following ions entering into the neuron?
A. Calcium
B. Sodium
C. Magnesium
D. Glycine
E. Potassium
Calcium
Excitotoxicity is a process that can lead to neuronal death due to excessive accumulation of the excitatory neurotransmitter glutamate, which then activates NMDA receptors. This overactivation leads to a pathological increase of intracellular calcium, which then activates multiple downstream effectors to cause apoptosis of the neuron. Although glycine can also activate NMDA receptors similar to glutamate, it does not actually enter the cell through these channels. Sodium, potassium, and magnesium are not primarily involved in NMDA excitatory signaling.
Which of the following conditions is caused by damaged or missing proteins at the neuromuscular junction?
A. Hereditary spastic paraplegia
B. Myasthenia gravis
C. Duchenne muscular dystrophy
D. Nemaline myopathy
E. Polymyositis
Myasthenia gravis
Myasthenia gravis is an autoimmune disorder characterized by antibodies directed against nicotinic cholinergic receptors, impairing transmission across the neuromuscular junction and resulting in early fatigability. Duchenne muscular dystrophy is an X-linked recessive condition that results in loss of expression of dystrophin, a protein that links the sarcolemma to the outermost myofilaments. Loss of dystrophin results in myofiber necrosis and easy muscle fatigability. Polymyositis is an inflammatory condition characterized by infiltration of muscle fibers by T cells with subsequent necrosis. Nemaline myopathies are characterized by rod-shaped structures noted on electron microscopy along the Z-disks of the sarcomere. The affects the orderly structure of the sarcomere, impairing efficient contraction. Hereditary spastic paraplegia results in progressive difficulty with ambulation and spasticity related to various inheritance patterns of mutations that converge on axonal viability of corticospinal tracts and fasciculus gracilis fibers.
Which of the following channels opens in response to GABAB receptor activation?
A. Potassium
B. Magnesium
C. Water
D. Chloride
E. Calcium
Potassium
GABAB receptors are metabotropic receptors that get activated by GABA to stimulate the opening of potassium channels in order to decrease the neuronal membrane potential. This hyperpolarizes the neuron and makes it less likely to fire an action potential, which in turn reduces the amount of neurotransmitter released by the neuron. Therefore, GABAB receptors are known as inhibitory receptors. On the other hand, GABAB receptors inactivate voltage-gated calcium channels to further reduce chances of action potential. GABAA receptors are ligand-gated chloride channels which also lead to hyperpolarization when activated. Magnesium channels and water pores are not greatly affected by GABAB receptor activation.
Which of the following proteins can be used as a marker of primitive neuroepithelial cells?
A. Nestin
B. Vimentin
C. S100
D. Glial fibrillary acidic protein
E. Tau
Nestin
Nestin, which is short for neuroepithelial stem cell protein, is a structural intermediate filament protein present in neuroepithelial stem cells in both the embryo and the adult brain. Glial fibrillary acidic protein (GFAP) is a marker for tumors of glial origin (ie. astrocytoma, oligodendroglioma). Tau is a protein that serves to support the stability of microtubules within neuronal axons, and it is found in excess in certain neurodegenerative diseases, such as Alzheimer’s disease. Vimentin is an intermediate filament important for supporting the cytosol of several different tissue types and useful as a tumor marker for several CNS tumors (i.e. astrocytoma, gliosarcoma, ependymoma). S100 is a protein present in cells derived from neural crest cells, and present as a tumor marker
for serval CNS tumors (ie. astrocytoma, schwannoma, choroid plexus tumors).
Which of the following is the mechanism of action of botulinum toxin?
A. Blockage of presynaptic voltage gated calcium channels
B. Degradation of acetylcholine
C. Blocking acetylcholine receptors
D. Inhibiting acetylcholinesterase
E. Inhibition of presynaptic release of acetylcholine
Inhibition of presynaptic release of acetylcholine
Botulism impairs vesicular release of acetylcholine into the neuromuscular junction. The toxin binds to the terminal and is endocytosed. A portion of this toxin becomes cytosolic and cleaves SNARE proteins that are responsible for docking of acetylcholine containing vesicles along the intracellular cell membrane. Lambert-Eaton myasthenic syndrome is characterized by antibodies against voltage gated calcium channels in the presynaptic membrane, resulting in decreased release of acetylcholine. Myasthenia gravis is characterized by antibodies against acetylcholine receptors, and diagnosis and treatment may include the use of acetylcholinesterase inhibitors, such as edrophonium or neostigmine.
Which of the following innervates the intrafusal fibers of the muscle spindle?
A. Aδ
B. α
C. C
D. B
E. Aγ
Aγ
Intrafusal muscle fibers are a component of the muscle spindle that are innervated by Aγ afferents that transmit information on stretch. Aδ afferents are slower conducting peripheral nerves from free endings of excessive stretch, temperature, pain (fast) and light touch. Type C sensory afferents are the slowest conducting peripheral nerves and convey temperature and pain (slow). Type B fibers are preganglionic sympathetic efferents in the ventral root. α motor neurons are efferent fibers that stimulate extrafusal skeletal fibers to result in contraction.
While undergoing a posterior cervical fusion, a patient becomes tachycardic, with an increase in end-tidal CO2 and a rapid increase in temperature. The first-line therapy for this condition has which of the following mechanisms of action?
A. Inhibition of presynaptic release of acetylcholine
B. Inhibition of calcium release from the sarcoplasmic reticulum
C. Blocking acetylcholine receptors
D. Inhibiting acetylcholinesterase
E. Blockage of presynaptic voltage gated calcium channels
Inhibition of calcium release from the sarcoplasmic reticulum
Dantrolene is a treatment for malignant hyperthermia as it decouples muscle fiber excitation and contraction. Dantrolene inhibits calcium release from the sarcoplasmic reticulum by antagonizing ryanodine receptors. As a result, troponin C continues to inhibit myosin binding to actin. Botulism impairs vesicular release of acetylcholine into the neuromuscular junction. The toxin binds to the terminal and is endocytosed. A portion of this toxin becomes cytosolic and cleaves SNARE proteins that are responsible for docking of acetylcholine containing vesicles along the intracellular cell membrane. Lambert-Eaton myasthenic syndrome is characterized by antibodies against voltage gated calcium channels in the presynaptic membrane, resulting in decreased release of acetylcholine. Myasthenia gravis is characterized by antibodies against acetylcholine receptors, and diagnosis and treatment may include the use of acetylcholinesterase inhibitors, such as edrophonium or neostigmine.
Which of the following is considered the major inhibitory neurotransmitter in the human brain and spinal cord?
A. GABA
B. Dopamine
C. Acetylcholine
D. Serotonin
E. Histamine
GABA
GABA is the primary inhibitory neurotransmitter in the central nervous systems. Acetylcholine is the primary neurotransmitter of the parasympathetic nervous system and has excitatory effects causing dilation of blood vessels, contraction of smooth muscle, and promoting secretions. Dopamine plays an important role in regulating movement, most importantly within the substantia nigra, with dysfunction causing Parkinson’s disease. Unlike GABA, dopamine is an excitatory neurotransmitter. Additionally, epinephrine and histamine are not inhibitory neurotransmitters and regulate body homeostasis/flight-or-flight and inflammatory responses, respectively.
The organelle principally responsible for modification of synthesized membrane and secretory proteins is the:
A. Mitochondria
B. Endoplasmic reticulum
C. Lysosomes
D. Nucleolus
E. Golgi complex
Golgi complex
The golgi complex (golgi apparatus) is an important intracellular organelle responsible modification and packaging of proteins within the cell. The nucleus is the location where DNA is converted to mRNA, which in turn is used to produce proteins in the ribosomes on the endoplasmic reticulum where they are also packaged in vesicles. The golgi complex then takes up the proteins from the ribosomes, where they are modified and repackaged.
Dietary amino acids are critical for the synthesis of which of the following neurotransmitters?
A. Serotonin and Histamine
B. Serotonin and gamma-aminobutyric acid
C. Dopamine and gamma-aminobutyric acid
D. Gamma-aminobutyric acid and histamine
E. Dopamine and serotonin
**Serotonin and Histamine
**
Dietary amino acids are critical for the synthesis of neurotransmitters that require essential amino acids as the substrate of their synthesis. Essential amino acids cannot be produced by the body and, thus, must be obtained from dietary sources. Of the neurotransmitters listed, both serotonin and histamine require essential amino acids as the substrate of their synthesis. Serotonin can only be produced from tryptophan, and histamine can only be produced from histidine. The synthesis of dopamine can begin with the essential amino acid phenylalanine. However, the first step in the dopamine synthesis is conversion of phenylalanine to tyrosine by phenylalanine hydroxylase. Thus, dopamine can also be synthesized from tyrosine, a non-essential amino acid. Finally, gamma-aminobutyric acid is synthesized from glutamate, a non-essential amino acid.
The spatial and temporal restriction of excitation in the central nervous system is most commonly regulated by interneurons releasing which of the following neurotransmitters?
A. Epinephrine
B. GABA
C. Acetylcholine
D. Histamine
E. Dopamine
GABA
GABAergic interneurons play a vital role in creating a diverse network of neural connections and increasing the computational power of simple networks within the brain. GABA release inhibits excitatory neurons, allowing for downregulation of downstream effects. Acetylcholine is the primary neurotransmitter of the parasympathetic nervous system and has excitatory effects on dilation of blood vessels, contraction of smooth muscle, and to promote secretions. Dopamine plays an important role in regulating movement, most importantly within the substantia nigra, with dysfunction causing Parkinson’s disease. Unlike GABA, dopamine is an excitatory neurotransmitter. Additionally, epinephrine and histamine are not inhibitory neurotransmitters and regulate body homeostasis/flight-or-flight and inflammatory responses, respectively.
The electrical activity of two neurons is being recorded. Whenever Neuron One has action potentials, Neuron Two is less likely to have action potentials. This results from Neuron One releasing a neurotransmitter on Neuron Two that opens which of the following postsynaptic structures?
A. Sodium/Potassium pumps
B. Metabotropic receptors
C. Magnesium channels
D. Chloride channels
E. Potassium channels
Chloride channels
Since the firing of Neuron One reduces the probability of Neuron Two having an action potential, this Neuron One is an inhibitory neuron. In the central nervous system, one can broadly separate excitatory and inhibitory neurons into those releasing glutamate and GABA, respectively. Therefore, it is likely that the firing of Neuron One is triggering a release of GABA to the postsynaptic terminal of Neuron Two. Due to the rapid inhibition of Neuron Two, it is more likely that the released GABA is reaching GABAA receptors rather than GABAB since the latter produces its inhibitory signals in a slower and more prolonged fashion. Therefore, activation of GABAA receptors on Neuron Two is likely causing an opening of chloride channels, and thus hyperpolarizing the membrane potential to reduce action potential firing. The other choices (potassium channels, magnesium channels, sodium/potassium pumps, metabotropic receptors) are not primarily involved with the inhibitory firing from GABAA receptor activation.
Which of the following regions of the brain contains primarily GABAergic neurons?
A. Raphe nucleus
B. Globus pallidus
C. Locus coeruleus
D. Cortex
E. Subthalamic nucleus
Globus pallidus
Understanding the circuitry of the basal ganglia is necessary for understanding how the CNS modulates movement and for understanding movement disorders, such as Parkinson’s disease. GABA is neurotransmitter used by many of the nuclei within the basal ganglia, it is also the primary inhibitory neurotransmitter of the CNS. The globus pallidus is group of two nuclei (GPexterna (GPe) & GPinterna (GPi)) that project GABAergic neurons to the subthalamic nucleus (STN) and thalamus, respectively. The subthalamic nucleus contains primarily glutaminergic (excitatory) neurons. The locus raphe nucleus (serotonergic) and locus coeruleus (noradrenergic) are not part of the basal ganglia.
Which of the following enzymes is responsible for the rate-limiting step of dopamine synthesis?
A. Aromatic L-amino acid decarboxylase B. Phenylalanine hydroxylase
C. Tyrosine hydroxylase
D. Monoamine oxidase
E. Catechol-O-methyl transferase
Tyrosine hydroxylase
Dopamine synthesis occurs via a three step metabolic pathway involving three distinct enzymes. In the primary pathway, the initial substrate, L-phenylalanine, is converted to L-tyrosine by phenylalanine hydroxylase. Next, L-tyrosine conversion to L-DOPA is catalyzed by tyrosine hydroxylase, the rate-limiting step in the synthesis of dopamine. Finally, L-DOPA conversion to the active end product dopamine is catalyzed by aromatic L-amino acid decarboxylase. The primary pathways responsible for dopamine degradation to homovanillic acid involve enzymatic reactions by monoamine oxidase-A, monoamine oxidase-B, catechol-O-methyl transferase and aldehyde dehydrogenase.
An action potential occurs when a nerve membrane becomes relatively more permeable to which of the following?
A. Sodium
B. GABA
C. Calcium
D. Water molecules
E. Potassium
Sodium
Depolarization of a neuron occurs when an adequate stimulus causes the membrane potential to increase from resting membrane potential (-70mV) to the potential that will sufficiently activate voltage-gated sodium channels (approximately -55mV). Once this occurs, sodium channels convert from the closed to the open state and the cell depolarizes. Voltage-gated potassium channels have the opposite effect in that they are only activated once the membrane potential nears +30mV, and the potassium ions exit the cell which drives the membrane potential back down towards resting membrane potential. Influx of calcium ions is often the effect rather than the cause of an action potential, as it occurs once an action potential reaches the terminal to allow for release of neurotransmitter. Water molecules and GABA do not play a role in the initiation of an action potential.
Which of the following substances provides the energy for fast axonal transport?
A. Cytoplasmic ATP
B. Mitochondrial ATP
C. Cytoplasmic NAD
D. Vesicular NAD
E. Vesicular ATP
Vesicular ATP
Due to the significant length of neuronal axons and the need for rapid transport, neurons cannot rely on diffusion for the transport of cellular organelles and vesicles. Instead, neurons utilize a system of microtubules and proteins for axonal transportation. Microtubules serve as cytoskeletal tracks that run along the length of the axon and are composed of the protein tubulin. Motor proteins, known as kinesin and dynein, then serve to transport different types of cargo along the microtubular network.
The axonal transport proteins require ATP for energy. The majority of cellular ATP is produced via glycolysis within the mitochondria. However, the mitochondria are not evenly distributed along the length of neuronal axons, therefore are an unreliable source of ATP for axonal transport proteins, which require a constant supply of ATP. Instead, glycolysis occurs on the vesicular membrane, utilizing GADPH, which is abundant throughout the cytosol, and resulting in local production of ATP.
Which of the following voltage-gated ion channels is most likely to cause the rising phase of the neuronal action potential?
A. Potassium
B. Chloride
C. Sodium
D. Calcium
E. Magnesium
Sodium
In order for a neuron to transmit an action potential, excitatory neurotransmitters bind to the cell body resulting in the opening of ligand-gated ion channels, such as sodium, if there is a net change in positively charged ions entering the cell body the membrane potential becomes more positive (depolarization). Once this change reaches a threshold potential, voltage-gated sodium channels open, resulting in a rapid influx of sodium ions and further depolarization, which is known as the rising phase (step 2 in the action potential figure). While other ion channels (ligand and voltage-gated) are involved in this process, it is the opening of the voltage-gated sodium channels that has the greatest effect on depolarization necessary for propagation of the action potential. Once a certain membrane potential is reached, the voltage-gated sodium channels become inactivated and voltage-gated potassium channels open, allowing the positively charged potassium ions to flow out of the cell body (repolarization; step 3 in the action potential figure).
Several antiepileptic medications, including phenytoin, carbamazepine, valproate, and lamotrigine act by binding preferentially to depolarized voltage-gated sodium channels. This results in a voltage-dependent inhibition of the sodium channels and prevents the spread of seizure activity.
EEG potentials in a normal person arise from which of the following?
A. The action potential of a single neuron in the region of the electrode
B. The difference in electrical potential between two electrodes
C. The summation of excitatory or inhibitory post-synaptic potentials for a network of synchronous neurons in the region of the electrode
D. The excitatory or inhibitory post-synaptic potential of a single neuron in the region of the electrode
E. The summation of action potentials for a network of synchronous neurons in the region of the electrode
**The summation of excitatory or inhibitory post-synaptic potentials for a network of synchronous neurons in the region of the electrode
**
The electric potential of a single neuron is too small to be directly monitored. Instead, the electrode records the summation of synchronous activity of network of neurons in the region of the electrode. It does not represent action potentials, which are too short to be recorded, but instead is the summation of excitatory or inhibitory post-synaptic potentials.
Which of the following classes of afferent fibers is responsible for the strong, brisk reflex elicited by tapping on a muscle or tendon?
A. Ia
B. II with non-spindle endings
C. IV
D. α
E. III
Ia
Non-contractile muscle spindle fibers are innervated by Ia sensory afferents conveying information of stretch and velocity, which excite efferent α motor neurons in the ventral horn. Type III and IV classes are slower conducting fibers that convey information of pain, temperature and chemical stimuli. Type II fibers with non-spindle endings are sensitive to deep pressure.
Which of the following results in the voltage dependence of the NMDA receptor?
A. Ca2+ blockade
B. Na2+ efflux
C. Ca2+ efflux
D. K+ influx
E. Mg2+ blockade
Mg2+ blockade
NMDA Receptors (NMDAR) are both voltage-gated and ligand-gated. Opening of ion channels requires both depolarization of the post-synaptic membrane and attachment of neurotransmitters glutamine and glycine. Magnesium ions rapidly and reversibly block open NMDA channels in a highly voltage-dependent manner. Magnesium ions block the opening of NMDAR when the membrane is not depolarized. Once glutamate allows for depolarization via binding with AMPA receptors, ion channels allow influx of Na+ and K+, depolarizing the cell. Then, glutamate and glycine can bind to NMDAR and allow for calcium ion permeability, which then allows for conformational changes that allow for more responsiveness to glutamate and an increase in AMPA receptors. Therefore, action potentials can propagate.
GABA-mediated inhibitory postsynaptic potentials act at inotropic receptor-gated channels for which of the following ions?
A. Na+
B. Mg2+
C. Cl-
D. Zn2+
E. K+
Cl-
GABA receptors are Cl- ionophore pentamer complexes. GABA receptors respond to benzodiazepines, barbiturates, picrotoxin, and some anesthetic steroids. The GABA binding site allows for opening of the Cl- channel. Flow of negatively charged ions inhibits the post-synaptic cells and prevents further depolarizations because the Cl- ion flow makes the cells more negatively charged than the neuronal firing threshold.
The other ions listed have roles in resting membrane potential and stabilization of cell membranes but do not contribute to inhibitory postsynaptic potentials in GABA receptors.
In the signaling mechanisms underlying long-term potentiation, calcium/calmodulin-dependent protein kinase II and protein kinase C are activated by the process of calcium entering the cell through which of the following receptors?
A. NMDA receptor
B. Glycine receptors
C. Kainate receptor
D. GABAB receptor
E. AMPA receptor
NMDA receptor
The induction of long-term potentiation (LTP) begins when a post-synaptic neuron is depolarized. This depolarization causes dislodging of the magnesium ions that were blocking the NMDA receptor and therefore allows many calcium ions to flow into the cell to activate the downstream effectors of LTP. AMPA and kainate receptors are also involved in LTP on the post-synaptic neuron but involve the inflow of sodium and the outflow of potassium. Interestingly, activation of NMDA receptors leads to the actual insertion of AMPA receptors into the postsynaptic membrane. While glycine has been shown to induce LTP through activation of synaptic NMDA receptors, calcium ions still flow through the NMDA receptors rather than glycine receptors. GABAB receptors do not play a major role in LTP.
Which of the following proteins acts as the motor for retrograde axonal transport toward the cell body?
A. Dynein
B. Tubulin
C. Myosin
D. Actin
E. Kinesin
Dynein
Due to the significant length of neuronal axons and the need for rapid transport, neurons cannot rely on diffusion for the transport of cellular organelles and vesicles. Instead, neurons utilize a system of microtubules and proteins for axonal transportation. Microtubules serve as cytoskeletal tracks that run along the length of the axon and are composed of the protein tubulin. Motor proteins, known as kinesin and dynein, then serve to transport different types of cargo along the microtubular network. Kinesin is responsible for anterograde transport, whereas dynein is responsible for retrograde transport. This is clinically important, as dysfunction of dynein has been noted as important in the development of several neurodevelopmental and neurodegenerative conditions, such as amyotrophic lateral sclerosis. Alzheimer’s disease, and Huntington’s disease.
Which of the following mechanisms is responsible for ion channel gating?
A. Removal of the sodium-potassium pump
B. Direct permeability of the cell membrane
C. Conformational changes of receptor subunits
D. Increase in number of ion receptors
E. Destruction of the extracellular binding domains
Conformational changes of receptor subunits
All ion channels that have been extensively studied have two or more stable conformational states. Gating refers to the transition of a channel between different states. In general, ion-gated channels are comprised of multiple subunits that will coordinate twisting and bending to allow for conformational change and opening of the channel. Downstream effects vary according to the type of channel and can allow free flow of ions through the channel. Regulatory mechanisms are in place to control the amount of time a gate is active. This is done via ligand binding, phosphorylation/dephosphorylation, changes in membrane voltage, and/or stretch/pressure.
Which of the following best describes the role of calcium ions at the synapse?
A. Calcium efflux initiates binding of SNARE proteins between the synaptic vesicle and the pre-synaptic membrane
B. Calcium influx initiates binding of SNARE proteins between the synaptic vesicle and the pre-synaptic membrane
C. Calcium influx promotes unidirectional membrane depolarization along the axon
D. Calcium efflux promotes unidirectional membrane depolarization along the axon
E. Calcium influx results in membrane repolarization in response to the voltage change from opening of sodium channels
Calcium influx initiates binding of SNARE proteins between the synaptic vesicle and the pre-synaptic membrane
Action potential propagation occurs secondary to unidirectional membrane depolarization via voltage-gated sodium channels. As the signal nears the terminal end of the axon, this depolarization results in the opening of voltage-gated Ca++ channels and subsequent Ca++ influx.
The intracellular calcium initiates the binding of SNARE (soluble NSF attachment protein receptors) proteins on the synaptic vesicle (synaptobrevin) and the presynaptic membrane (syntaxin and SNAP-25). The SNARE proteins then allow for exocytosis of and release of neurotransmitters from the synaptic vesicle into the synaptic cleft.
At the presynaptic membrane, which of the following ion movements is most critical for release of neurotransmitters?
A. Cl-
B. Ca2+
C. Na+
D. K+
E. Mg2+
Ca2+
Presynaptic neurotransmitter release is primarily modulated by calcium ions. After an action potential is achieved, an influx of Ca2+ ions via voltage-gated Ca channels activates vesicular exocytosis via binding to SNARE protein complexes (Soluble N-ethylmaleimide-sensitive factor activating protein receptor) at presynaptic releasing sites.
Sodium and potassium channels are crucial for the resting membrane potential, action potential, and hyperpolarization; however, they do not directly play a role in vesicular neurotransmitter release.
Which of the following structures is required for synaptic vesicles to release neurotransmitters?
A. SNARE proteins
B. Ligand-gated sodium channels
C. Myosin
D. Dynein
E. Kinesin
SNARE proteins
Depolarization of the presynaptic neuro via an action potential results in the influx of calcium ions via voltage-gated calcium channels. The calcium initiates the binding of SNARE (soluble NSF attachment protein receptors) proteins on the synaptic vesicle (synaptobrevin) and the presynaptic membrane (syntaxin and SNAP-25). The SNARE proteins then allow for exocytosis of and release of neurotransmitters from the synaptic vesicle into the synaptic cleft. Notably, botulinum neurotoxins inhibit the SNARE proteins at the neuromuscular junction resulting in paralysis.
The absolute refractory period limits which of the following?
A. Opening of voltage-gated potassium channels
B. Switch of voltage-gated sodium channels from the closed state to the inactive state
C. Activation of ligand-gated potassium channels
D. Depolarization
E. Repolarization
Depolarization
Depolarization of a neuron occurs when an adequate stimulus causes the membrane potential to increase from resting membrane potential (-70mV) to the potential that will sufficiently activate voltage-gated sodium channels (approximately -55mV). Once this occurs, sodium channels convert from the closed to the open state and the cell depolarizes (reaches +30mV). Once a sodium channel opens, it is then converted into the inactive state in which no further stimulus can cause it to open – i.e. the absolute refractory period. This is the brief time period where no depolarization can occur until enough sodium channels convert back from the inactive state to the closed state until another stimulus causes them to once again open. The reason that the neuron can only depolarize to approximately 30mV is this is the threshold where voltage-gated potassium channels are opened to drive the membrane potential back to an overall negative value. Therefore voltage-gated potassium channels can be opened during the absolute refractory period. Ligand- gated potassium do not play a large role in the neuronal actional potential.
Which of the following ions is responsible for blocking the ion pore at the NMDA glutamate receptor at resting membrane potential?
A. Potassium
B. Magnesium
C. Sodium
D. Chloride
E. Bicarbonate
Magnesium
NMDA receptors (NMDA-R) are a type of glutamate-gated ion channel. Glutamate is the primary excitatory neurotransmitter in the CNS and plays a critical role in several processes including neuroplasticity, learning, and memory. The NMDA-R is unique in several ways, including its need for a co-agonist (glycine) as well as the role of Magnesium (Mg++) blockade. The extracellular concentration of Mg++ is higher in the extracellular space, which drives Mg++ into the NMDA channel, blocking the passage of any other ions. When the cell is depolarized, the Mg++ ion is displaced from the channel, which allows for Ca++ & Na+ influx and K+ efflux from the cell. Ketamine is a dissociative anesthetic and common recreational drug that acts by inhibiting the NMDA receptor.
Demyelination causes which of the following effects on voltage-dependent channels and axonal conduction velocity?
A. Inhibition of voltage-dependent channels and decreased conduction velocity
B. Inhibition of voltage-dependent channels and increased conduction velocity
C. Diminished activation of voltage-dependent channels and no effect on conduction velocity
D. Diminished activation of voltage-dependent channels and decreased conduction velocity
E. Diminished activation of voltage-dependent channels and increased conduction velocity
**Diminished activation of voltage-dependent channels and decreased conduction velocity
**
Action potential propagation is dependent on sequential opening and closing of voltage-gated sodium channels along the length of the axon. In an unmyelinated nerve, these channels are spaced evenly along the length of the axon. In myelinated nerves, conduction is also dependent on the sequential opening and closing of voltage-gated channels; however, they are not evenly distributed. The sodium channels are clustered in the areas between myelin in the nodes of Ranvier and relatively sparse within the myelinated segments. Conduction is possible between the segments, because the myelin increases the axon’s membrane resistance and decreases the membrane capacitance, which prevents the flow of the positive ions out of the axon. This allows the signal to reach and activate the next cluster of voltage-gated sodium channels and perpetuate the action potential.
When an axon undergoes demyelination, it is unable to simply act as an unmyelinated nerve, because the distribution of voltage-gate channels remains unchanged. Without myelin, the axonal membrane resistance decreases, and the capacitance increases. This results in a loss of positive ions across the membrane in-between the clusters of voltage-gated channels and requires greater change in ion concentration to stimulate the voltage-gated sodium channels. The combination of these changes results decreases the activation of the voltage-gated channels. In a pure demyelinating process, conduction still occurs, and therefore the amplitude remains relatively unchanged, however the velocity is slowed.
Which of the following drugs blocks the uptake of dopamine into synaptic vesicles?
A. Amytriptyline
B. Pramipexole
C. Risperidone
D. Entacapone
E. Tetrabenazine
Tetrabenazine
Among the catecholamine neurotransmitters, dopamine is unique in that it is completely synthesized in the cytosol of the neuron and requires uptake into synaptic vesicles. In contrast, norepinephrine and epinephrine are synthesized within the synaptic vesicles. In order for dopamine to be released as a neurotransmitter into the synaptic cleft, it must first be transported from the cytosol into the synaptic vesicle, and this process is performed by vesicular monoamine transporters (VMAT). Tetrabenazine is a VMAT2 inhibitor used for the treatment of Huntington disease. By inhibiting VMAT2, tetrabenazine depletes storage of dopamine for use as a neurotransmitter.
Risperidone is an antipsychotic medication also used for the treatment of Huntington disease; however, it works as dopamine and serotonin receptor antagonist.
Entacapone is a COMT inhibitor, which decrease the breakdown of dopamine from the synaptic cleft and is used in the treatment of Parkinson’s disease.
Amitriptyline is a tricyclic antidepressant that increases the synaptic concentration of serotonin and norepinephrine by inhibiting their re-uptake.
Pramipexole is a dopamine receptor (D2) agonist used in the treatment of Parkinson’s disease.
The arrival of an action potential at the presynaptic terminal triggers neurotransmitter release through an opening of which of the following voltage-gated ion channels?
A. Magnesium
B. Chloride
C. Calcium
D. Potassium
E. Sodium
Calcium
Action potential propagation occurs secondary to unidirectional membrane depolarization via voltage-gated sodium channels. As the signal nears the terminal end of the axon, this depolarization results in the opening of voltage-gated Ca++ channels. The subsequent influx of Ca++ in the presynaptic neurons triggers synaptic vesicles to fuse with the pre-synaptic membrane and release their neurotransmitters into the synaptic cleft.
