PHRM 290 Exam 3 With Correct Solution
What is the most common second messenger? - ANSWER Ca++
What are the concentration gradients for Ca++?
Outside:
Inside:
Intracellular stores: - ANSWER Outside: Hi
Inside: low
Intracellular stores: Hi
TRP, NMDA, PX2, RyR, and VDCC receptors are all examples of - ANSWER Ca++
permeable ion channels
VDCC are widely distributed where? - ANSWER excitable cells
VDCC have increased activity from - ANSWER membrane potential depolarization
What does Ca signalling enable cells to do? - ANSWER couple electrical activity to
intracellular Ca++ signals
Prolonged elevations of intracelluar Ca++ triggers what? - ANSWER inactivation to
prevent cytotoxicity
What are the subunits of VDCC? - ANSWER pore-forming: alpha-1 subunits
accessory: Beta, alpha2- epsilon, gamma, calmodulin, CaM
What subunit interacts with Ca and is thought to underlie Ca dependent VDCC
interactions? - ANSWER CaM
VDCC are blocked by - ANSWER heavy metals like La3+, Ni2+, Cd2+, Mn2+
What opens VDCC? - ANSWER depolarization from an action potential
α2-δ subunits are linked by - ANSWER disulfide bonds
what is the regulatory function of α2-δ subunits? - ANSWER increase Ca++ channel
currents by increasing the surface channel density and enhanced activation.
α2-δ subunits are targets for the drugs - ANSWER pregabalin and gabapentin
What are pregabalin and gabapentin used for? - ANSWER treatment of neuropathic pain
,Pregabalin has a trade name of - ANSWER Lyrica
What is Lyrica used for? - ANSWER chronic pain disorders such as diabetic nerve pain
or spinal cord injuries
β subunits are responsible for? - ANSWER cytosolic regulatory subunit that enhances
VDCC activity. These subunits speed up the rate of channel activation and cause a
hyperpolarizing shift.
β subunits also modulate - ANSWER trafficking of alpha 1 subunit by binding to the ER
retention site.
γ subunits are responsible for - ANSWER decreasing Ca++ channel activity
what are the two types of γ subunits and where are they found? - ANSWER γ 1 - skeletal
muscle
γ 2- brain
Do all VDCC have γ subunits? - ANSWER no
what does a defect in γ2 contribute to? - ANSWER epilepsy
what subunit determines the major functional characteristics and defines the channel
subtype? - ANSWER alpha 1
what is the structure of alpha one subunit? - ANSWER - 4 repeated domains that are
connected via cytoplasmic linkers
- each domain has 6 membrane spanning helices (S1-S6)
- the S5-S6 region from the pore
what are the two major groups of VDCC? - ANSWER High voltage activated (HVA)
Low voltage activated (LVA)
What group do T type VDCCs belong to? - ANSWER LVA
What genes encode for T- type VDCCs? - ANSWER 3.1, 3.2, 3.3
What does LVA mean? - ANSWER the channel activation occurs near resting membrane
potential (ie a low threshold)
How fast or slow is T type VDCC inactivation? - ANSWER rapid
Do LVA VDCCs have accessory subunits? - ANSWER no, only HVA
T type VDCC blocker - ANSWER Kurtoxin (main one) , Nickel, Mibefradil
What gene codes for N-type VDCCs? - ANSWER CaV 2.2
, N-type VDCC,
HVA or LVA?
Fast or Slow inactivation? - ANSWER HVA, Slow inactivation
What selectively blocks N type VDCCs? - ANSWER ω-conotoxins GVIA and MVIIA
Where are N type VDCCs located? What are they involved in? - ANSWER presynaptic
nerve terminals, they are involved in neurotransmitter release and pain perception
Calcium dependent neurotransmitter release - ANSWER An increase in Ca++ drives the
release of neurotransmitters.
What is the synthetic form of ω-conotoxins MVIIA? - ANSWER Ziconotide, trade name is
prialt
What is prialt used for? how is it administered? - ANSWER It is used as a pain reliever for
chronic pain and must be administered intrathecally.
P/Q Type calcium channels are coded by what gene - ANSWER CaV 2.1
Are P/Q type VDCCs:
HVA or LVA?
Fast or Slow inactivation? - ANSWER HVA, Slow inactivation
P-type VDCC:
Located:
Blocked by:
Involved in: - ANSWER Located: in the presynaptic nerve terminals, neuromuscular
junction
Blocked by: ω-agatoxin IVA and ω-conotoxin MVIIC
Involved in: NT release
Q-type VDCC:
Located:
Blocked by:
Involved in: - ANSWER Located: in cerebellar granular cells and pyramidal neurons
Blocked by: Blocked by: ω-agatoxin IVA (more sensitive than P-type) and ω-conotoxin
MVIIC.
What is the most common second messenger? - ANSWER Ca++
What are the concentration gradients for Ca++?
Outside:
Inside:
Intracellular stores: - ANSWER Outside: Hi
Inside: low
Intracellular stores: Hi
TRP, NMDA, PX2, RyR, and VDCC receptors are all examples of - ANSWER Ca++
permeable ion channels
VDCC are widely distributed where? - ANSWER excitable cells
VDCC have increased activity from - ANSWER membrane potential depolarization
What does Ca signalling enable cells to do? - ANSWER couple electrical activity to
intracellular Ca++ signals
Prolonged elevations of intracelluar Ca++ triggers what? - ANSWER inactivation to
prevent cytotoxicity
What are the subunits of VDCC? - ANSWER pore-forming: alpha-1 subunits
accessory: Beta, alpha2- epsilon, gamma, calmodulin, CaM
What subunit interacts with Ca and is thought to underlie Ca dependent VDCC
interactions? - ANSWER CaM
VDCC are blocked by - ANSWER heavy metals like La3+, Ni2+, Cd2+, Mn2+
What opens VDCC? - ANSWER depolarization from an action potential
α2-δ subunits are linked by - ANSWER disulfide bonds
what is the regulatory function of α2-δ subunits? - ANSWER increase Ca++ channel
currents by increasing the surface channel density and enhanced activation.
α2-δ subunits are targets for the drugs - ANSWER pregabalin and gabapentin
What are pregabalin and gabapentin used for? - ANSWER treatment of neuropathic pain
,Pregabalin has a trade name of - ANSWER Lyrica
What is Lyrica used for? - ANSWER chronic pain disorders such as diabetic nerve pain
or spinal cord injuries
β subunits are responsible for? - ANSWER cytosolic regulatory subunit that enhances
VDCC activity. These subunits speed up the rate of channel activation and cause a
hyperpolarizing shift.
β subunits also modulate - ANSWER trafficking of alpha 1 subunit by binding to the ER
retention site.
γ subunits are responsible for - ANSWER decreasing Ca++ channel activity
what are the two types of γ subunits and where are they found? - ANSWER γ 1 - skeletal
muscle
γ 2- brain
Do all VDCC have γ subunits? - ANSWER no
what does a defect in γ2 contribute to? - ANSWER epilepsy
what subunit determines the major functional characteristics and defines the channel
subtype? - ANSWER alpha 1
what is the structure of alpha one subunit? - ANSWER - 4 repeated domains that are
connected via cytoplasmic linkers
- each domain has 6 membrane spanning helices (S1-S6)
- the S5-S6 region from the pore
what are the two major groups of VDCC? - ANSWER High voltage activated (HVA)
Low voltage activated (LVA)
What group do T type VDCCs belong to? - ANSWER LVA
What genes encode for T- type VDCCs? - ANSWER 3.1, 3.2, 3.3
What does LVA mean? - ANSWER the channel activation occurs near resting membrane
potential (ie a low threshold)
How fast or slow is T type VDCC inactivation? - ANSWER rapid
Do LVA VDCCs have accessory subunits? - ANSWER no, only HVA
T type VDCC blocker - ANSWER Kurtoxin (main one) , Nickel, Mibefradil
What gene codes for N-type VDCCs? - ANSWER CaV 2.2
, N-type VDCC,
HVA or LVA?
Fast or Slow inactivation? - ANSWER HVA, Slow inactivation
What selectively blocks N type VDCCs? - ANSWER ω-conotoxins GVIA and MVIIA
Where are N type VDCCs located? What are they involved in? - ANSWER presynaptic
nerve terminals, they are involved in neurotransmitter release and pain perception
Calcium dependent neurotransmitter release - ANSWER An increase in Ca++ drives the
release of neurotransmitters.
What is the synthetic form of ω-conotoxins MVIIA? - ANSWER Ziconotide, trade name is
prialt
What is prialt used for? how is it administered? - ANSWER It is used as a pain reliever for
chronic pain and must be administered intrathecally.
P/Q Type calcium channels are coded by what gene - ANSWER CaV 2.1
Are P/Q type VDCCs:
HVA or LVA?
Fast or Slow inactivation? - ANSWER HVA, Slow inactivation
P-type VDCC:
Located:
Blocked by:
Involved in: - ANSWER Located: in the presynaptic nerve terminals, neuromuscular
junction
Blocked by: ω-agatoxin IVA and ω-conotoxin MVIIC
Involved in: NT release
Q-type VDCC:
Located:
Blocked by:
Involved in: - ANSWER Located: in cerebellar granular cells and pyramidal neurons
Blocked by: Blocked by: ω-agatoxin IVA (more sensitive than P-type) and ω-conotoxin
MVIIC.
