Calcium channels II Flashcards
What is the alpha1 subunit of a calcium channel similar to?
VG Na+ channel–> except for a few AA changes in a few key domains
Subunits of a VG Ca2+ channel?
Alpha1&2, Beta, gamma, delta
What are the accessory subunits of a VGCa2+ channel?
a2, beta, gamma, delta
Role of accessory subunits in a VGCa2+ channel
Trafficking of receptors to cell surface
Common ancestor of Ca2+ Na+ channels?
NaChBac–> bacterial VG Na2+ channel
How many genes make up the alpha1 subuit?
10
Where are the regulatory sites for VGCa2+ channels?
C terminal domains
Examples of regulatory sites on VGCa2+ channels?
Second messenger binding sites, protein phosphorylation sites, calmodulin association sites, sites for interaction w. SNARE complex
How many domains make up the alpha 1 subunit?
4 homologous domains
How many membrane segments does each domain of the a1 subunit have?
6
Which membrane segment of each domain of the a1 subunit is the voltage sensor?
S4
Order of size for bits of a Ca2+ VG channel?
Membrane segments make up homologous domains which make up the a1 subunit
Which membrane segments of each domain of the a1 subunit are the pore loop?
S5 and S6
Which membrane segments of each domain of the a1 subunit determine ion conductance?
S5, S6
What were the different alpha1 subunits originally defined based on?
Electrical properties of channels
How are the different alpha 1 subunits defined currently?
Genetically–> in terms of homology
Two main subdivisions of VGCa2+ channels?
High Voltage Activated ( HVA, -40 - -10 mV)
Low Voltage Activated (LVA, -60 - -70 mV)
Diff types of HVA VGCa2+ channels?
L, N, P/Q and R type
L type HVA VGCa2+ channels?
“L”ong lasting, slowly inactivating currents (>500ms)
Not particularly involved in control of vesicular transmitter release
Opened by depolarisaiton to drive caclcium transience–> to recruit proteins that work with calcium
N type HVA VGCa2+ channels?
“N”euronal, slowly inactivating
P/Q type HVA VGCa2+ channels?
“P”urkinje, P slowly inactivating, Q variable
R type HVA VGCa2+ channels?
(IVA) – R (follows Q, Resistant) – slow / medium inactivation
Main subtypes of VGCa2+ channels found on nerve terminals, coupling to release?
N, P/Q, R
Diff types of LVA VGCa2+ channels?
T-type
T type LVA VGCa2+ channels?
“T”ransient, rapidly inactivating
Specialist–> not as widely identified in nerve terminals
How can different VGCa2+ channels be distinguished between?
Their sensitivity to a range of toxins
Which toxin are P/Q HVA VG Ca2+ channels sensitive to?
agatoxin
Which toxin are N HVA VG Ca2+ channels sensitive to?
conotoxin
Which toxin are R HVA VG Ca2+ channels sensitive to?
SNX-482
What are L type VGCA2+ channels a target for?
Therapeutic drugs
Therapeutic drugs that target L type VGCa2+ channels?
Benzodiazepines, dihydropyridines
