BIO 2420 Exam 2
List the events, in their correct order of occurrence, that occur during chemical synaptic transmission (see Slide #4 of Part Two).
1. Action potentials reach axon terminals 2. Voltage gated Ca2+ channels open 3. Ca2+ binds to the sensor protein in cytoplasm 4. Ca2+ protein complex stimulates fusion and exocytosis of neurotransmitter 5. Presynaptic depolarization (usually by an action potential) 6. Presynaptic Ca2+ influx through voltage gated Ca2+ channels 7. Exocytosis of neurotransmitter containing synaptic vesicles 8. Binding of neurotransmitter to postsynaptic receptors 9. Change in postsynaptic membrane conductance and voltage 10. Diffusion, degradation, and/or reuptake of neurotransmitter 11. Synaptic vesicle membrane retrieval and recycling
What are the THREE STATES of voltage-gated sodium channels (VGNCs)?
1. Closed and ready to open 2. Open and conduction Na+ ions 3. Inactivated (similar to the the open state, but is non conducting)
How fast (i.e., at what speed or velocity) can APs propagate?
100 meters/second
How many volts is a millivolt?
10^-3 volts, or 1/1000 of a volt
Approximately how WIDE is the synaptic cleft? Give the units of measurement.
12-20 nanometers across
The adult human brain receives about __% of cardiac output.
15%
Approximately HOW MANY different structures or regions of the human brain are labelled in SLIDE #14?
19
What percentage of cells in the brain are neurons?
20%
The adult human brain weighs approximately _ to ___ pounds.
3 to 3.5
How many transmembrane alpha helices are present within the alpha subunit of a voltage-gated sodium channel (VGNC or VGSC)?
6 alpha helices
The cerebral cortex composes approximately ________ % of the adult human brain.
80%
What percentage of cells in the brain are glial cells?
80%
How much neurotransmitter is typically secreted by a single bouton at Central Synapses?
A very small amount, as little as one synaptic vesicle per action potential.
A bunch of neuronal cell bodies right next to each other within the brain, that all have the same or a related functions, is known as a ______________________________.
Basal ganglia
A complex interaction of inhibition and excitation within the _______________ _____________ is involved in a lot of our motor control.
Basal ganglia
Parkinson's disease involves problems within the _______________________ region of the brain.
Basal ganglia
Why is it crucial that potassium leak channels in the PM are constitutively-open?
Because potassium ions constantly diffuse across the plasma membrane through K+ leak channels.
Why does the peak of an action potential overshoot 0 mV?
Because voltage is transiently heading for ENa+
What brain structure is responsible for motor control & motor memories? Hint: this structure performs body control, and stores motion memories.
Insula
The parietal lobes are important for (choose one): emotional control, interpretation of sensory input, vision or language?
Interpretation of sensory input
Which specific component of the extracellular fluid is present within the synaptic cleft?
Interstitial fluid
What is the range of magnitudes (in millivolts) of the resting membrane potential (RMP) of human cells?
Between -20 mV and -100 mV
Are humans radially symmetrical, or bilaterally symmetrical?
Bilaterally
How do local anesthetics block pain? What is the molecular mechanism?
Block inner mouth of VGNCs in sensory neurons to prevent Na+ ion conduction (no pain signal can be sent to brain). Prevent the sensory nerves from telling the brain that you are in pain.
How does Saxitoxin affect the function of VGNCs?
Blocks VGNCs using a mechanism similar to block by TTX
What is the function of the Thalamus?
It is a relay center between the motor cerebral cortex and other brain areas.
WHY do APs propagate in only one direction once they are triggered? Why don't they reverse directions once they have started?
It is unidirectional due to fast, spontaneous inactivation of VGNC, which prevents the AP from reversing its direction of propagation.
What does the intracellular III-IV loop of VGNCs have to do with fast, spontaneous channel inactivation?
It prevents the AP from reversing its direction of propagation.
How will the RMP change if the extracellular potassium concentration ([K+]) increases by 2-fold (i.e., doubles)?
It will become depolarized due to the increase in equilibrium potential of potassium.
Extracellular K+ concentration is maintained at ~ 5 millimolar by the _________________.
Kidneys
The Basal Ganglia are made up of a bunch of ________________________________________.
Nuclei (a bunch of neurons right next to each other with the same function)
A single motor neuron cell body within the spinal cord forms chemical synapses with (approximately how many) presynaptic terminals?
Numerous. About ??
The type of glial cell that forms the myelin coating of neurons within the CNS:
Oligodendrocytes
Electrical gradients (such as the transmembrane voltage or RMP) only affects what kind of molecules?
Only charged molecules (like cations or anions)
How does Brevetoxin affect the function of VGNCs?
Persistently activates the channel and causes the repetitive firing of the nerves
What is acetylcholinesterase, precisely where (at the neuromuscular junction) is it located, and what specific function does it perform?
• Acts as an excitatory neurotransmitter at the NMJ • Acetylcholinesterase (AChE; an enzyme) within the synaptic cleft rapidly hydrolyzes secreted ACh into choline and acetate. • The liberated choline is taken-up by the presynaptic terminal and combined with acetyl-CoA to synthesize more ACh (the enzyme which catalyzes this reaction is choline acetyltransferase). • Increase the surface area ??
Name two different toxins that are produced by marine plankton (dinoflagellates) and that may become concentrated in the flesh of filter-feeding marine shellfish (e.g., clams and mussels) during a Red Tide, and can poison animals?
Saxitoxin, brevetoxin
What is the specific cellular location of the receptor proteins for water-soluble neurotransmitter molecules?
plasma membrane
The sensory area of the cortex is located posterior to the __________ _____ sulcus.
postcentral gyrus
CSF is thought to be formed by __________ rather than ultrafiltration.
secretion
Ions in solution a surrounded by a cloud of water molecules which form the ion's ______ __ _________.
sphere of hydration
What does the EDF tell you regarding the various physiological ions?
it tells which direction across the PM an ion can move passively without the input of energy, and which direction energy is required to move the ion across the PM.
Action potentials (APs) travel ____ __________ and trigger ___________ __ ____ ________.
long distances, neurosecretion by axon terminals
The type of glial cell that covers the outside wall of capillaries of the CNS and induces the blood-brain barrier:A
strocytes
Many drugs produce their effects by altering ________ ____________.
synaptic transmission
The RMP has a high Electrical Field Strength, because the plasma membrane is very ____.
thin
The cavity (i.e., lumen) within the embryonic Neural Tube will become the _________ in the adult brain.
ventricles
APs are created by the transient opening of ________-gated ___ channels.
voltage, Na+
The posterior pituitary gland is an extension of the ______________.
hypothalamus
How does myelination alter the amount of energy that axons must expend pumping sodium ions (Na+) out of the cytoplasm?
Decreases the metabolic energy expenditure by the neuron, because the Na+/K+ pumps don't need to transport as much Na+ and K+ following an AP.
What does an Association Neuron do?
Give the ability to control impulsive (automatic) responses
Why does gray matter look gray, and white matter looks white?
Gray matter is unmyelinated neurons and white matter is myelinated axons.
The most basic physiological functions (e.g., digestion & heart function) are regulated by the (forebrain, midbrain or hindbrain)?
Hindbrain
The temporary (transient) positive feedback that occurs at the threshold potential is known as the _______ Cycle.
Hodgkin
Which brain structure is very important in maintaining body temperature (part of homeostasis), osmolarity and circadian rhythms?
Hypothalamus
Why (i.e., what is the function of) are there junctional folds of the sarcolemma at a neuromuscular junction?
In addition to the housekeeping functions of a cell plasma membrane, the sarcolemma is directly involved in synaptic transmission, action potential propagation, and excitation-contraction coupling.
How does the selectivity-filter of an ion-selective channel remove the water molecules from an ion?
In some channels, there are spaced, charged parts of the channel pore substitute exactly for water molecules and allow the permeating ion to leave them behind. (pore architecture)
How does myelination affect the velocity of AP propagation?
Increases the propagation velocity of APs.
Can a function that resides in one cerebral hemisphere (e.g., mathematical reasoning; logic) be moved to the other hemisphere? In other words, is lateralization plastic?
Yes, it is plastic
How many presynaptic terminals form chemical synapses with a single skeletal muscle fiber?
1
In humans, axons can exceed _ meter in length.
1
What is the definition of 'threshold potential'?
A critical level to which a membrane potential must be polarized to initiate an action potential. Likelihood of an AP being triggered is 50%
Which specific (and relatively simple) tools did the Spanish scientist & physician Santiago Ramon y Cajal use to demonstrate the existence of the synaptic cleft, and that the nervous system is composed of distinct, separate cells rather than a continuous reticulum?
A microscope and artistic drawings
What specific electrical event is usually responsible for opening the voltage-gated Calcium channels within the plasma membrane of a presynaptic terminal?
Action potential
Why are APs described as being 'non-decrementing'?
Amplitude of waveform does not decrease as the AP propagates along the length of the axon
When VGNCs are in the inactivated state and the transmembrane voltage is +40 mV, where are the voltage-sensing S4 segments positioned in relation to the cytoplasm?
Away from cytoplasm and close to extracellular space
Who invented The Black Reaction?
Camillo Golgi
Which specific part of the alpha subunit of a VGNC serves as the 'inactivation gate'?
Central channel
What body fluid compartment is produced by the Choroid Plexuses?
Cerebral Spinal Fluid
From which naturally-occurring drug are Local Anesthetics derived?
Cocaine
Which specific transmembrane proteins and protein structures connect adjacent cells at electrical synapses?
Connexons
What does the Cerebrum do? What's it function? How many neurons and synapses are in the cerebrum?
Controls thoughts, actions, and higher brain functions. Divided into 4 lobes, frontal, parietal, occipital, and temporal. Contains roughly 16 billion neurons.
Neurotransmitter X binds to and activates an ionotropic receptor that conducts only potassium ions across the plasma membrane of the postsynaptic cell. Is the effect of neurotransmitter X on the postsynaptic cell going to be excitatory or inhibitory?
Inhibitory
Which of the three layers (above) will roll up into a tube to become the nervous system?
Ectoderm
A 22-day old human embryo consists of three layers of cells: what are they?
Ectoderm, mesoderm, and endoderm
The frontal lobes of the cerebral cortex are important for (choose one): executive function, emotional control, interpretation of sensory input, vision or language? Choose all correct answers.
Emotional control
_________ cells line the ventricles of the brain and they ALSO cover tufts of capillaries to form the CHOROID PLEXUSES (See Table 7.2).
Ependymal
Through which specific cellular, phospholipid bilayer-trafficking process are synaptic vesicles secreted?
Exocytosis
Are synaptic clefts intracellular or extracellular?
Extracellular
What condition (depolarization or repolarization?) causes voltage-gated sodium channels (VGNCs) to enter the OPEN STATE from the CLOSED STATE?
Fast depolarization
Thinking (i.e., cognition) is a function of the hindbrain, midbrain or forebrain?
Forebrain
The temporal lobes are important for (choose one): emotional control, interpretation of sensory input, vision, language?
Language, hearing, memory
What are the three structures within the brainstem? What are their relative positions?
Medulla oblangata (bottom), pons (middle), and the midbrain (top)
The Electrochemical Driving Force (EDF) on an ion is proportional to the absolute difference between the ________ _________ and the ______ ________ for that ion.
Membrane potential, Nernst Potential
Which specific membrane transport protein is responsible for maintaining a high intracellular concentration of K+?
Na+/K+ pumps
Is the inside of the cell electrically negative, or electrically positive, RELATIVE to the extracellular fluid?
Negative
What are fixed intracellular anions? Precisely where are they located? How do they influence the RMP?
Negatively charged molecules, confined within the cell, they interact with the positively charged cations on the extracellular side of the plasma membrane
What does an Autonomic Motor Neuron do?
Nerve that stimulates contraction (or inhibits contraction) of smooth muscle and cardiac muscle and that stimulates glandular secretion.
What does a Somatic Motor Neuron do?
Nerve that stimulates contraction of skeletal muscles
At many chemical synapses, neurotransmitter molecules such as acetylcholine are water-soluble (i.e., hydrophilic). How are such neurotransmitters typically stored inside cells? Where inside cells are they stored? NOTE: neurotransmitters such as acetylcholine and dopamine are usually loaded into synaptic vesicles. In contrast, in non-vesicular secretion (as is thought to occur in taste cells), ATP simply diffuses out of the cytosol through the CALHM1 channels).
Neurotransmitters such as acetylcholine and dopamine are loaded into synaptic vesicles, but in non-vesicular secretion ATP simply diffuses out of cytosol through CALHM1 channels (taste receptor cells)
In the inactivated state, can the channel conduct sodium ions (Na+) across the plasma membrane?
No
CALHM1 is a candidate for a protein that mediates (choose the correct answer: vesicular secretion, non-vesicular release or retrograde release?) of ATP into a synaptic cleft between a taste receptor cell and a sensory neuron.
Non-vesicular secretion
Why does the presynaptic terminal of a spinal motor neuron secrete a 3-fold excess of acetylcholine onto a skeletal muscle fiber? (This means that only one third of the amount of ACh that is secreted would be sufficient to trigger the muscle fiber to contract.)
Physiologically ensures the muscle fibers always contracts in response to an action potential arriving at the presynaptic terminal.
Hyperkalemia is when blood _________ concentration is too high (i.e., elevated).
Potassium
The RMP is mostly created by the constant diffusion of ______________ ions in ____ directions across the ______ ____________.
Potassium (K+), both, plasma membrane
Why does the peak of an AP occur at less positive voltages when the extracellular sodium concentration is reduced?
Reduces electrochemical driving force on Na+ and lowers Nernst (equilibrium) for Na+
List three (3) molecules that are known to undergo retrograde release from the postsynaptic cell.
Retrograde release of a lipid-soluble molecule from the postsynaptic cell or the release of nitric oxide (NO) gas from the postsynaptic cytoplasm • Endogenous cannabinoids, anandamide, 2-arachidonoyl glycerol
What does the Black Reaction show?
Reveals details of a neurons fine structure
What medical condition has been treated by a corpus callosotomy? Can a person still function AFTER one of their cerebral hemispheres is surgically removed (radical hemispherectomy)?
Seizures and yes they can still function
Two kinds of cells found within Dorsal Root Ganglia are:
Sensory neurons ?? Satellite cells (glial cells, not schwann cells)
Within a presynaptic terminal, what is a 'synaptic vesicle'?
Small secretory vesicle that contains a neurotransmitter, is found inside an axon near the presynaptic membrane, and releases its contents into the synaptic cleft after fusing with the membrane
If the myelination is completely removed from an axon (as can occur in the human disease known as multiple sclerosis or MS), what will happen to action potential propagation? Will it continue, or will it fail? Why or why not?
Sodium will leak out before it gets to the next node. AP will fail to propagate along the axons in the places where the myelination has been lost.
At a chemical synapse, what is a terminal "bouton"?
Specialized presynaptic terminal at the end of an axon. Contain necessary organelles, proteins and molecules needed to transmit chemical/electrical information to the postsynaptic cell.
Which alpha helix within each transmembrane domain (i.e., repeats) serves as the voltage-sensing mechanism of the channel?
The 4th alpha helix (S4 segment)
Lateralization means _________________________________________.
There are certain things on either side of the brain. for example, left side has logic and reasoning, while right side has facial recognition.
What are the NUCLEI within the Hypothalamus? What do they do?
They are a group of neuronal cell bodies or neuronal somata. Control specific aspects of homeostasis (temperature control, water balance, hunger, satiety, circadian rhythms and reproduction).
Where exactly is the motor cortex located?
The back of the frontal lobe
Where exactly is the somatosensory cortex located?
The front of the parietal lobe
What is Loligo? Why was it useful and important in the early study of action potentials?
The giant axon of the marine squid. Led to the understanding of action potentials.
Why are potassium (K+) leak channels in the plasma membrane important for establishment of the RMP?
The membrane potential of a resting neuron is primarily determined by the movement of K+ ions across the membrane. The RMP is mostly created by the constant diffusion of potassium ions (K+) in both directions across the plasma membrane.
What specific feature of the plasma membrane allows extracellular ions to electrostatically interact with fixed intracellular anions?
The plasma membrane is very thin (less than 5nm)
What is the relationship between the Hypothalamus, and the Posterior Pituitary gland?
The posterior pituitary is an extension of the hypothalamus and is formed from embryonic ectoderm
At which type of synapse are chemical neurotransmitter molecules secreted or released into the synaptic cleft (usually, but not always) through the process of exocytosis by the presynaptic cell?
The presynaptic nerve terminal (the end of the axon)
What are Schwann Cells and what material do they form around axons?
They are glial cells that render AP saltatory. Myelin coating is what they form within the peripheral nervous system and go around the axons numerous times.
What is a Choroid Plexus?
Thin, highly-vascularized, transporting epithelial structures that protrude into the ventricles.
What is special about the Initial Segment of an axon (i.e., the Axon Hillock)?
This is where the action potential is triggered. The threshold for action potentials is lower due to an extremely high concentration of voltage-gated sodium channels.
In order for voltage-gated sodium channels (VGNCs) to recover from inactivation (i.e., re-enter the closed-and-ready-to-open state) following an action potential, they require two conditions. What are they?
Time and negative membrane potential
Why do VGNCs need to have three states? Why can't they just have OPEN and CLOSED states?
To make sure that the AP travels unidirectionally and can't go backwards.
What is tetrodotoxin? Name some animals that contain it. How does it block action potentials? How is the mechanism of block different from that produced by local anesthetics?
Toxin found in pufferfish, blue ringed octopus, rough skinned newt, and moon snail; blocks transmission of AP by blocking extracellular mouth of VGNC pore
What does a Sensory Neuron do?
Transmits impulses from the sensory receptor into the CNS
The relatively large amount of surface area dedicated to your fingers within the somatosensory cortex is related to the importance of having high sensitivity of touch within your fingers? True or false?
True
True or False? For a typically-sized cell having a total plasma membrane surface area of 1 centimeter squared, only a tiny fraction of the total number of potassium ions within the cytoplasm must become unequally distributed across the plasma membrane in order to establish a resting membrane potential (RMP) of -70 mV.
True
It is important that the RMP be relatively large and negative (e.g., -90 mV) BECAUSE this large, negative transmembrane voltage is important for keeping ______________________ in the closed-and-ready-to-open state.
VGNCs
Into which cavity do the Choroid Plexuses protrude?
Ventricles ??
The occipital lobes are important for (choose one): emotional control, interpretation of sensory input, vision or language?
Vision
The electrochemical gradient for potassium (K+) is determined by two forces: what are they?
Voltage across the PM divided by the thickness of the PM
How do you calculate the Electrical Field Strength of the RMP?
Voltage divided by the distance across which it exists.
Functional magnetic resonance imaging (fMRI) enables you to see __________________________within the brain during activity.
blood flow? function?
The primary motor cortex is located anterior to the _______ sulcus.
central
The outer layer of the ________ is known as the cerebral cortex.
cerebrum
The connection of nerves in between the two hemispheres of the cerebrum is known as the:
corpus collosum
What does it mean that AP propagation along a myelinated axon is 'saltatory'?M
eans the AP appears to jump from node to node because it can, in fact, occur only at the nodes.
The Nernst Equation describes the transmembrane voltage that will exist when K+ is in ____________ _________.
electrochemical equilibrium
When diffusion of an ion (e.g., K+) across the plasma membrane in response to the transmembrane voltage is equal-and-opposite to diffusion of the same ion in response to the concentration gradient across the PM, the ion is said to be in _____________ __________.
electrochemical equilibrium
Name four (4) different types of GLIAL CELLS within the CNS, and tell what they do.
• Astrocytes: form the blood-brain barrier • Oligodendrocytes: form myelination • Microglia: eat invaders and debris • Ependymal cells: line the ventricles and form choroid plexuses
What are the potential fates of neurotransmitters after they have entered a synaptic cleft?
• Diffuse away from/out of cleft (= dilution) • Degraded by enzymes present within synaptic cleft • Reuptake (via specialized transporter proteins) into the presynaptic terminal • Uptake (via specialized transporter proteins) into surrounding glial cells
What specific types of neurotransmitter receptor or transporter proteins are affected by THC, Xanax, Oxycontin, Hydrocodone, caffeine, nicotine, Angel Dust, heroin, morphine?
• Ionotropic glutamate receptors (angel dust) • Metabotropic cannabinoid receptor (THC) • Metabotropic opioid receptors (Oxycontin and Hydrocodone, heroin and morphine) • Increases the sensitivity of ionotropic GABAa receptors to their natural agonist, the neurotransmitter GABA (xanax) • Ionotropic nicotinic acetylcholine receptors (nicotine) • Metabotropic adenosine receptors (caffeine)
What are the differences between an ionotropic neurotransmitter receptor, and a metabotropic neurotransmitter receptor?
• Ionotropic neurotransmitter receptors have built-in (integral) ion channel and neurotransmitter binding site. (aka ligand-gated receptors, chemically-gated receptors, or neurotransmitter-gated receptors.) Metabotropic neurotransmitter receptors have a binding site, but do not have an integral ion channel. • Metabotropic receptors may indirectly open or close ion channels in the postsynaptic membrane by activating an intracellular signaling pathway.
What are the differences between a receptor LIGAND, a receptor AGONIST, and a receptor ANTAGONIST?
• Ligand: means to bind. Any molecule that binds to a receptor protein • Agonist: any ligand that activates the receptor • Antagonist: any ligand that prevents the receptor from being activated • Competitive antagonist: binds to the same site on the receptor protein as the agonist • Non competitive antagonist: binds to a different site on the receptor protein as the agonist
What are three (3) functions of cerebrospinal fluid (CSF)?
• Provides shock absorption • Supplies nutrients • Removes wastes produced by metabolic processes within brain cells
Name five (5) different types or classes of molecules known to function as neurotransmitter molecules.
• Small molecules: acetylcholine (Ach), adenosine triphosphate (ATP), nitric oxide (NO - this is a gas) • Amines: epinephrine (E), norepinephrine (NE), dopamine (DA), serotonin • Amino Acids: gamma-aminobutyric acid (GABA), glycine, glutamate and aspartate • Peptides: somatostatin (SST)*, beta-endorphin, arginine vasopressin (AVP), insulin, glucagon, calcitonin • Lipids: anandamide, 2-arachidonoylglycerol (2-AG)
List five (5) different ion channels, and their order of opening, that are involved in neuromuscular transmission and excitation-contraction coupling in skeletal muscle.
• Voltage-gated Ca2+ channels (VGCCs) in motor neuron plasma membrane • Nicotinic AChRs in the sarcolemma of the postsynaptic muscle fiber • Voltage-gated Na+ channels (VGNCs) in the sarcolemma • VGCCs in the T-tubules (they mechanically open RyR1) • Ca2+ release channels (Ryanodine Receptors 1 or RyR1) in the bilayer of the sarcoplasmic reticulum
