Calcium Channels Flashcards
Overall structure of channels
Alpha 1 subunit forms TM pore.
Alpha 2 delta is extracellular unit
Beta is intracellular
Alpha 1 subunit structure
4 TM domains, each with S1-S6 units.
S4 is voltage sensor
Between S5 and S6 is Ca2+ selective filter
Beta subunit
4 isoforms B1-B4
Binds to alpha domain
Enhances trafficking of alpha to membrane
Increases current amplitude and shift activation Ca entry
Alpha 2 delta
Enhances trafficking of alpha.
Delta part anchors to membrane, Alpha 2 is extracellular
Where does Gabapentin bind to?
Alpha 2 delta subunit
L type activation threshold
High
L type subtypes
Ca v 1.1 - 1.4
L type blocked by
Nifedipine, Verapamil
N type
High activation threshold, Main source for nerve terminal transmitter release
N type irrevesibly blocked by
w-conotoxin GV1A (irreversibly blocks pores). From cone shell mollusc
Drug used to block N type
Ziconotide. Used for neuropathic pain
P/Q type function
Nerve terminal transmitter release
P/Q type blocked by
w-Agatoxin IVA. From funnel web spider, activation gating inhibitor
Where are R type found
Neurons and dendrites
R type blocked by
SNX-482, from Tarantulas. Activation gating inhibitor
T type function and found
Low voltage activated, fast inactivation, Found in cardiac pacemakers ad well as in the brain
T type numbers and location
- 1 - Neuronal, cardiac
- 2 - Neuronal
- 3 - Neuronal
T type selectively blocked by
mibefradil
Other T type blockers - 4
Carbamazepine, phenytoin also block Na channels
Ni 2+ blocks Ca v 3.2 selectively
Ethosuximide - also blocks Na channels
TTA-A2, TTA-P2 - Novel ones
