Exam 1 Flashcards
what is a receptor?
the component of the cell that interacts with a drug (exogenous) or endogenous ligand to produce a response
what are the 2 properties of receptors?
- recognition - the receptor must exist in a state that allows a drug/ligand to bind [saturable (limited # of receptors on cell); specific (similar drugs/ligands produce similar effects; often stereoselective (+)/(-) forms, only one is active, other is control); reversible (dissociation); reconstitution of the receptor (expression in cell line)]; 2. transduction - binding of agonist must produce a response
what are the receptor types?
- channel-linked receptors (signal binds, channel opens, ions flow across membrane); 2. enzyme-linked receptors (signal binds, enzyme activated (phosphylation), enzyme generates product); 3. GPCRs (signal binds, Gprotein binds, Gprotein activated); 4. intracellular receptors ie. hormone receptors (signal binds, activated receptor regulates transcription)
why are synapses important sites in neuropharmacology?
neurons use chemicals to talk to each other. Neuropharmacologists can mimic transmitters to mimic or stop actions
what is the difference between a DRC & a concentration-response curve?
- DRC measures the functional response to a drug/ligand (typically in vivo). It is what is given. However, lots of things happen when a drug is given i.e metabolism, biotransformation so we don’t actually know the concentration; 2. concentration-response curves is typically in vitro in a dish bc it is the concentration of a drug at the receptor site.
what is an agonist?
ligand that causes a response. Increasing concentrations should cause an increase in response
what is a full agonist?
ligand that causes maximal response. Instrinic activity=1
what is a partial agonist?
ligand that causes a response less than that of a full agonist (no stabilization of the conformation of the receptor to give a full response). Intrinisc activity between 0 and 1
what is an antagonist?
ligand that does not cause a response. It blocks the response to an agonist. Intrinisc activity=0. can be reversible or irreversible
what is an e-max?
concentration of ligand that produces a maximal response
what is an EC50?
concentration of a ligand that produces half-maximal response
what is efficacy?
measure of the relative maximal response between drugs AKA effectiveness
what is potency?
measure of how much drug is needed to produce a response
which would you rather have, an agonist with high potency/low efficacy or an agonist with low potency/high efficacy?
low potency/high efficacy
what are competitive receptor antagonists?
binds to the same site on the on the receptor as the agonist; shifts the concentration response curve to the right (EC50 is higher); no change in Emax; decrease in potency, but not in efficacy
how can you compete away the effect of a competitive receptor antagonist?
by adding more agonist
what are non-competitive antagonists?
binds to the same site as the agonist but is irreversible; can also bind to a different site-allosteric modulator; prevents the receptor from producing a response; decreased Emax & efficacy
how can you compete away the effect of a non-competitive receptor antagonist?
you can not compete away the effect of the antagonist by adding more agonist
what are allosteric, non-competitive drugs?
binding somewhere else but may interfere with receptor response; change in conformation of binding site can look like non-competitive antagonists; can also increase the effects of agonists
what is constitutive activity?
receptors that can be active in the absence of any bound ligand
what do inverse agonists do?
shuts off constituitively active receptor
give 2 examples of constituitive receptor activity
- opiates can; 2. cannabinoids definitely because they are in the membrane surrounded by lipids
cannabinoid antagonists are not really antagonists, but what?
inverse agonists
what are radioligand binding assays?
used to measure affinity of a ligand for a receptor
what are the 3 basic radioligand binding experiments?
- saturation binding experiments; 2. competition binding experiments; 3. kinetics experiments
you can determine the affinity of agonists and antagonists, but what can’t you do with that information?
you can not differentiate the affinities btwn the two
besides affinity, what kind of information can radioligand binding assays provide?
total number of available receptors, whether ligands act at similar receptors, can compare affinities btwn ligands
the affinity for drug X for its receptor is 2nM, what is the efficacy?
you don’t know. All you know is that 2nM is what it takes to bind 50% of receptors in the population. You are not measuring a response to know whether it is an agonist or antagonist. You are only meauring binding. NO RESPONSE=NO EFFICACY!!
what is a Kd?
the equilibrium dissociation constant; the concentration of the ligand required to bind 50% of receptors
what is the inverse of Kd?
affinity
what is fractional occupancy?
used to calculate the percentage of receptors bound at any concentration
what kind data do saturation binding graphs provide?
Kd (affinity) and Bmax (max amt of receptor binding)
which segment of the spinal cord matches up with the vertebrae?
cervical
what are the segments of the spinal cord?
cervical, thoracic, lumbar, sacral, & coccygeal segments, filum terminale, cauda equina
what makes up the white and gray matter of the spinal cord?
white matter is composed of myelin; gray matter is composed of cell bodies, dendrites, axon terminals, helper cells i.e. glia
T/F…a nerve i.e. sciatic nerve is just a single nerve
FALSE…a nerve is a bundle of nerves
sensory (afferent) info comes into the ____ part of the spinal cord, while motor (efferent) info comes into the ____ part of the spinal cord.
dorsal; ventral
sensory & motor info come into the spinal cord (together/separately)
together
what type of cell bodies live in the intermediate cells of the spinal cord?
autonomic preganglionic fibers that go out to the periphery i.e effects BP, blood vessels, GI, etc
when sensory info comes in, they form branches. What are those branches called?
collaterals
how can one distinguish a cervical cross section of the spinal cord from the other segments?
by the presence of 2 bumps visible at the midline on the dorsal side of the spinal cord
what is the cortical spinal tract (upper motor neurons)?
information from the cortex for movement crosses at the end of the brain stem & synapses onto to lower motor neurons in the ventral horn
what is the name of the area in the cervical spinal cord designated for the leg called?
fasciculus (“tract”) gracilis (“leg”)
what is the name of the area in the cervical spinal cord designated for the hand called?
fasciculus (“tract”) cuneatus (“hand”)
how do neurons in the fasciculus cuneatus find their 2nd order neurons?
one neuron comes in and goes straight to the brain stem.
when does the primary order sensory neuron cross during touch?
the primary order sensory neuron does not cross until it finds its secondary order neuron in the caudal medulla. From there, it goes to the homonculus
what is the purpose of second order neurons in the spinal cord?
cell bodies for pain and noxious temperature; neurotransmitter released
when does the primary order sensory neuron cross for pain?
sensory info crosses where it comes in
what is the anterior funiculus for?
motor functions
the layout of a cross section of the cervical spinal cord is exactly the same in all segments. However, there is an exception. What is it?
the hand tracts (fasciculus cuneatus) is unique to the cervical segment. Other segments are smooth
in the autonomic system, where do cell bodies of the preganglionic fibers live?
in the intermediate gray
the sympathetic branch of the autonomic nervous system comes out of where?
the thoracic and lumbar segments of the spinal cord
where do the fibers of the sympathetic branch go to?
the sympathetic chain ganglion (SCG)
the DRG is (close to/far away from) the SCG?
close to
the preganglionic fibers of the sympathetic branch are (short/long) and release what on which receptors?
short; Ach; nicotonic receptors
the postganglionic fibers of the sympathetic branch are (short/long) and release what on which receptors?
long; NE; alpha & beta receptors
what is the sympathetic branch of the autonomic nervous system known as?
fight or flight
what is the parasympathetic branch of the autonomic system known as?
rest and digest
the preganglionic fibers of the parasympathetic branch are (short/long) and release what on which receptors?
long; Ach; nicotinic receptors
the postganglionic fibers of the parasympathetic branch are (short/long) and release what on which receptors?
short; Ach; muscarinic receptors
the gray matter is on the (inside/outside) of the cortex, and does what?
outside; send & receive info
what is sulci and gyri?
sulci are the grooves; gyri are the bumps of the cortex
what are the 3 components of the brain stem?
medulla, pons, midbrain (from bottom to top)
pyramid upper motor neurons are found where and do what?
found in medulla; comes down from cortex and must go through brain stem (motor)
what is so special about the portion of the 4th ventricle that is in the medulla?
that portion of the medulla is surrounded by a lot of gray matter
what nuclei are in the medulla, and what are their functions?
fasciculus gracilis & nucleus gracilis (touch, leg); fasiculus cuneatus & nucleus cuneatus (touch, arm); trigeminal tract & nucleus (pain, head); spinothalamic tract (pain, leg & arm); pyramind UMN (motor); hypoglossal nucleus (tongue, motor); solitary tract & nucleus (visceral afferents); inferior olivary nucleus (motor; huge nuclei; info across to cerebellum for coordination); raphe nucleus (serotonin); medial lemniscus (2nd order, touch)
how can you tell that you are looking at the pons?
it will be connected to cerebellum & you won’t see much of the pyramid UMNs
what nuclei are in the pons, and what are their functions?
cerebellar nucleus; spinothalamic tract (pain); pyramid UMN (motor); medial lemniscus (2nd order touch); facial nerve & nucleus
what nuclei are in the midbrain, and what are their functions?
medial geniculate nucleus (auditory); superior colliculus (vision); aqueduct (CSF; connects 3rd & 4th ventricle; PAG surrounds it (involved in pain & awareness)); medial lemniscus (touch); spinothalamic tract (pain); cerebral peduncle (motor); VTA (DA, reward); substantia nigra (motor, loss of DA here-> PD); red nucleus (motor); PAG (pain & defensive behavior)
what are the lobes of the brain & what are their functions?
frontal lobe (social behavior, language production, primary motor); parietal lobe (primary somatosensory, language comprehension); occipital lobe (vision); temporal lobe (memory, emotions, auditory); cerebellum (coordination)
what happens when a person has a stroke on the L side of their brain in the parietal lobe (wernicke’s area)?
they can no longer comphrend language; gibberish speech
what happens when a person has a stroke on the L side of their brain in the temporal lobe?
auditory deficits on both sides; can’t tell where sound is coming from
what happens when a person has a stroke on the L side of their brain in their frontal lobe (broca’s area)?
can still comphrend language (can still read) but can not produce words ex. Gabby Gifferds
why are some areas of homunculus larger than others?
due to amount of brain innervation
the part of the homunculus that spans the parietal lobe is (sensory/motor)
sensory info crosses where it comes in
the part of the homunculus that spans the frontal lobe is (sensory/motor)
motor
what role does the frontal lobe play in general, and also specifically?
in general, the frontal lobe is the higher association area responsible for motor and executive functions; specifically, the frontal lobe is composed of the orbital (flavor- tastes, smell, textures, temperature, mood); triangular (broca’s), & the operculum
what lobes comprise the polymodal area of the brain?
parietal, occipital, & temporal lobes
name 2 effects that are associated with a stroke in the polymodal area of the brain.
- POT (motion) - difficulty distinguishing motion ex. Determining whether a car is moving or not; 2. POT (hemineglect) - ignore the L side of the world & even the opposite side of their body
what role does the insula play?
taste, internal “gut” feelings, pain, disgust
what role does the limbic lobe play?
contains ACC & amygdala; learning, higher cognitive function, decision-making
what role does the corpus callosum, hypothalamus, thalamus, & brainstem play?
corpus callosum (connects hemisphere); hypothalamus (involuntary function); thalamus (relay station); brainstem (involuntary function)
electricity depends on the flow of ____.
charged particles (ions)
charge is measured in _____
coulombs- C
_____ is defined as the movement of charge in a given period of time.
current
the units of current are _____.
amperes (A)
the size or amplitude of a current is determined by the ________ and the _______.
potential difference between the electrodes; electrical conductance of the medium between them.
_____ is the amount of potential energy per unit of charge at a given location.
electrical potential
______ is the difference in potential between 2 locations (the work needed to move a test charge from one point to another).
potential difference
potential difference is measured by ____.
voltage (V)
______ is the ease of flow of current between 2 points, which is measured in _____.
conductance; Siemens (S)
_____ is the inverse of conductance and is measured in _____.
resistance; ohms (?)
conductance and resistance can be calculated if _____ and _____ are known.
potential; current
what is ohm’s law?
voltage (V)= current (I) * resistance ( R ) OR current (I)= conductance (g) * voltage (V)
what is a capacitor?
2 conductors (solution inside and outside the cell) separated by an insulator (membrane).
what happens when a charge is introduced to one of the conductors of a capacitor?
it pushes similar charges away from the other conductor (repel), creating a separation of charge
______ is a measure of how much charge (Q) needs to be transferred from 1 conductor to another to set up a given potential difference.
capacitance
____ are the units of capacitance.
farads (F)
why do all cell membranes have the same capacitance (1 æF/cm2)?
because all cell membranes are about the same thickness
the bigger the cell membrane, the (smaller/larger) the capacitor, and the (less/more) charges stored.
larger; more
once the charge separation occurs across the capacitor, why is there still no voltage?
because no current is flowing through the capacitor (ohm’s law)
what is the Na+/K+ ATPase channel composed of?
2 subunits (?, ?)
the Na+/K+ ATPase channel transports ____ Na+ ions out for every ___ K+ ions it transports in.
3; 2
how does the Na+/K+ ATPase channel work?
- ATP-bound pump binds 3 intracellular Na+ ions; 2. following ATP hydrolysis, the cytoplasmic loop of the pump is phosphoylated and ADP is released; 3. pump changes conformation which and exposes and releases Na+ ion s to the outside of the cell; 4. pump binds 2 extracellular K+ ions and the ?subunit dephosphoylates; 5. ATP binds the pump which causes a change in conformation to original state and K+ ions are released inside cell
after activation by a stimulus, the membrane potential ____ towards 0 mV due to the influx of ____. The membrane potential then returns to rest (-70 mV) due to the efflux of ___. This entire process is the ____.
depolarizes; Na+; K+; action potential
the resting membrane potential is due to what 2 factors?
- separation of ions across the cell membrane (creates ion gradients with pumps such as the Na+/K+ ATPase pumps); 2. permeability of the membrane to those ions
at rest, the cell membrane is substantially more permeable to ___ than to ____ due to more ___ channels being open.
K+; Na+; K+
at the equilibrium potential for a given ion, the current for that ion is ____.
0
for a positively-charged ion, if the membrane potential is more positive than the equilibrium potential, the direction of flux is ____.
out of the cell
for a positively-charged ion, if the membrane potential is more negative than the equilibrium potential, the direction of flux is ____.
into the cell
name an exception to ohm’s law.
when V= the equilibrium potential
how do you account for the exception to ohm’s law?
modify ohm’s law to account for the concentration gradient (V- Veq= IR)
the farther away from the equilibrium potential the membrane voltage is, the (smaller/larger) the current will be for that ion.
larger
changing the concentration of an ion on either side of the membrane will change the equilibrium potential, but not the slope of the current voltage plot. The bigger the concentration of ions, the bigger the voltage, which shifts the slope to the ____.
right
what is the goldman-hodgkin-katz equation?
modification of the nerst eq. to include the relative permeability’s (P) of each ion (Vm = RT/F ln (P(ion 1) [ion 1]o + P(ion 2) [ion 2]o / P(ion 1) [ion 1]i + P(ion 2) [ion 2]i) )
you are never going to be more negative than K+ (-100mV) because K+ is pulling it there. It is possible to get more positive than Na+, but how?
Ca2+ effects outside of the cell
____ is a rapidly propagated electrical message that moves along the axons of cells in the nervous system.
action potential
early researchers looked at seawater to help determine the dependence of ____ on the action potential.
Na+
____ is a technique in which the voltage is held at a desired potential and current flow across the membrane is measured.
voltage clamp
downward deflections in voltage-clamp recordings are (inward/outward) currents.
inward
inward currents are defined as the movement of (positive/negative) charge into the cell.
positive
upward deflections are outward currents which are movements of (positive/negative) charge out of the cell
positive
what can be used pharmacologically to separate Na+ and K+ currents?
tetrodotoxin (Na+ ch blocker) to lose inward current; tetraethylammonium (K+ ch blocker) to lose outward current
what is it called when the conductance of the membrane to Na+ and K+ increases as the membrane is depolarized?
rectification
the peak of the action potential is typically (above/below) Na+’s equilibrium potential.
below
what causes the undershoot in the action potential?
when more K+ ch’s are open than when at rest which brings it closer to K+’s equilibrium potential
when do Na+ ch’s begin to open?
when the generator potential is large enough for the cell to reach a membrane potential
___ is the time during which it is impossible to get another action potential and corresponds to the falling phase when Na+ chs are inactivated.
absolute refractory period
recovery of an action potential doesn_t occur until what happens?
hyperpolarization (more K+ chs opened)
___ is the time during which a strong stimulus can evoke another action potential and corresponds to after hyperpolarization when Na+ chs have recovered from inactivation.
relative refractory period
do all Na+ chs recover at the same time?
no
in the absence of ____, impulse propagation would not proceed over long distances
action potentials
why are large diameter, insulated axons better conductors?
large diameter axons have lower resistance = less leakage and longer conduction distances
if the membrane resistance is large or the axial resistance is small, what happens to the length constance?
it’s big which will cause the impulse to travel farther before it decays
if the capacitance is large, it takes (a long time/ a short time) to get the voltage shape.
a long time
why do myelinated axons move faster than unmyelinated axons?
under myelin, current is allowed to flow passively (no Aps). The more nodes (unmyelinated), the more you have to wait for conformational changes in Na+ chs opening which is slow; myelin increases membrane resistance -> increased length constant; myelin decreases capacitance -> decreased time constant
a high density of Na+ chs are found where on the cell?
initial segment (axon hillock)
why is impulse propagation unidirectional?
as the AP moves along the axon, the Na+ chs behind it become inactivated
what are the 3 important properties of ion chs?
- they conduct ions; 2. they recognize & select for specific ions; 3. they open & close in response to specific electrical, mechanical & chemical signals
why do currents get larger with depolarization?
more chs are open
why do currents get smaller as the voltage approaches the equilibrium?
decreased driving force
what gives a current its shape?
the summed activity of thousands of chs
what are the structural features of voltage-gated chs?
ion conducting pore; selectivity filter; voltage sensor; activation/inactivation gates
describe Na+ ch topology.
1 subunit with 4 domains (crosses 24x)
describe Ca2+ ch topology.
1 subunit with 4 domains
describe K+ ch topology.
4 subunits with 1 domain
describe the subunits of Na+ chs
_- main component of ch, ion conducting pore; _- accessory subunits, affects ch properties, target chs to membrane
describe the subunits of K+ chs
_- main component of ch, ion conducting pore, 4 individual subunits make functional chs; _- accessory subunits, affect ch properties, target chs to membrane
_subs alter the kinetics of what?
current
describe the subunits of Ca2+ chs
_1- ion conducting pore; 2, _, & _- accessory subs, ion ch properties, targeting to membrane; 2- target for antiepileptic drugs (gabapentin (Neurontin) & pregabalin (Lyrica))
how do drugs that bind to _2_subs of Ca2+ chs work?
prevents expression of _sub from getting to membrane-> less transmitter release-> less synaptic transmission-> less communication btwn neurons
ion chs select ions to flow through based on what?
atomic radius, surface density, hydrated ionic radius
___ allows 1 molecule of water to go through the pore with it, while ___ sheds its hydration shell when it goes through the pore.
Na+; K+
the pore of the ch _____ charge by creating an environment that is energetically favorable so ion flows through.
stabilizes
what causes Na+’s activation gate to open?
when the membrane potential depolarizes; S4 (voltage sensor) pulls S5 & S6 to open ch
describe K+ ch “n-type” inactivation.
residues in the cytosolic part of ch (n-terminus) plug pore (ball & chain)
describe K+ ch “c-type” inactivation.
mediated by collapse of the ion conducting pore near the selectivity filter
how do TTX & saxitoxin work?
block ion conducting pore of Na+ ch
how do veratridine, batrachotoxin, aconitine & grayanotoxin work?
prevents Na+ voltage sensor from moving properly
how does scorpion toxin & sea anenome toxin work?
inhibits Na+ inactivation
how do local anesthetics work?
block Na+ ch from inside pore
how can chs be regulated by lipids?
PIP2 presence or absence at the membrane can modulate ch activity
give an example of the modulation of Ca2+ chs by Gprotein __subs.
__sub of a somatostatin receptor inhibiting voltage-gated Ca2+ ch
how can kinases regulate ion chs?
phosphorylation leads to enhanced or inhibited function
what can you do to lose the block of TTX?
point mutation at the mouth of the pore
Na+ currents exhibit variable kinetics. TTX sensitive currents are (faster/slower) than TTX resistant currents.
faster
if a neuron is depolarized briefly and then hyperpolarized slightly, Na+ current can reactive a ____ current in cerebellar purkinje neurons and vestibular nucleus neurons. This is mediated by ___.
resurgent; _
Cav1 and Cav2 family members of Ca2+ chs require (smaller/larger) changes in voltage, while Cav3 requires (smaller/larger) changes.
larger; smaller
how do Ca2+ chs inactivate?
Ca2+ influx through ch activates Ca2+ binding protein (calmodulin) which promotes inactivation
how can Ca2+ inactivation be prevented?
EGTA prevents the increase in Ca2+ in the cell so it does not bind calmodulin; use of Ba2+ as a charge carrier to slow inactivation since it does not bind calmodulin
which type of K+ ch is contributes most to membrane repolarization?
Kv (delayed rectifier currents)
where are the delayed rectifier K+ chs expressed on the cell?
low voltage-activate: nodes/paranodes; high voltage-activated: soma, nodes, presynaptic; a-type: dendritic, presynaptic
what are a-type K+ currents?
transient outward currents; activates area of AP from (-) undershoot to the threshold so the cell has more time btwn spikes. This allows Na+ chs to recover from inactivation so that the 2nd AP is as consistent as the 1st
what are KCNQ/M-currents?
inhibition following activation of muscarinic Ach receptors via phospholipase C_-induced cleavage of PIP2 from membrane which closes KCNQ ch; does not inactive; dampens repetitive/burst firing
application of a KCNQ activator i.e. retigabine, shifts the voltage dependence to the (left/right), making it easier to open the chs.
left
what does the application of a KCNQ inhibitor do?
turns of hyperpolarizing influence; makes it easier for the cell to get to threshold
what is the role of Ca2+ activated K+ chs?
self-regulation; contribute to spike adaptation (slowing of spiking over time) or to burst firing; 3 types (BK, SK, IK); after-hyperpolarizations (undershoot)
how do voltage-gated Ca2+ and Ca2+-activated K+ chs cooperate to produce a spiking pattern?
- Ca2+ enters neuron through voltage-gated Ca2+ chs during AP; 2. high [Ca2+] inside neuron activates Ca2+ dependent K+ ch, stopping the cell from depolarizing; 3. [Ca2+] falls as Ca2+ ions are pumped out of cell, so K+ chs close & neuron depolarizes to spike threshold
what are CNG chs?
voltage-insensitive; non-selective (allows Na+ to enter & depolarize cell); found in visual & olfactory sys; gated by binding cAMP or cGMP
what are HCN chs?
hyperpolarization activated; makes it easier to get to threshold; pacemaker chs
describe CNG activation in photoreceptors.
- cGMP binds to CNG ch; 2. Na+ enters; 3. light hits retina & activates PDE which hydrolyzes cyclic nucleotides; 4. cGMP decreases which begin to close chs & signals that a photon has struck your retina
K+ATP chs are a target for what disease?
diabetes
how to K+ATP currents acts in _ cells of the pancreas in the presence of low glucose?
low glucose -> low ATP-> cell hyperpolarized bc the chs are open-> _cells are turned off & no insulin is released
how to K+ATP currents acts in _ cells of the pancreas in the presence of high glucose?
high glucose-> high ATP-> stop hyperpolarization-> cell depolarizes-> Ca2+ chs open & release insulin
what are two pore domain K+ chs?
voltage-insensitive; leaky K+ current that dominates resting membrane potential; TWIK; resistant to most K+ ch blockers; modulated by membrane stretch, temperature, acidosis, lipids, anesthetics
