L12 Flashcards
Ca.v (info)
open in response to depolaristion
Ca2+ is an important 2nd messenger used in muscle contraction, cell growth, synaptic transmission, gene expression, ion channels and protein kinases
only channels which directly convert electrical signals into biochemical work
High voltage activated Ca.v pore-forming subtypes
L-type
- Cav1.1 skeletal muscle
- Cav1.2 cardiac/smooth muscle
- Cav1.3 secretion form glands
P/Q-type - Ca2.1 CNS transmitter release
N-type - Cav2.2 PNS and CNS transmitter release
R-type - Ca2.3 transmitter release
Low voltage-activated Ca.v pore-forming subtypes
T-type
- Cav3.1, 3.2 and 3.3
all excitability of cells
Diversity in Ca.v channels
There is further diversity in Ca.v channels by adding ß and alpha2delta accessory subunits.n
Alpha1:ß:Alpha2Delta stoichiometry
ß interacts with alpha subunits between a1-a2
structure-wise its the same as K+, with Beta and an a2ß
Classical Calcium antagonists
L-type blockers:
- 1,4 dihydropyridines –> anti-hypersensitive
- phenylalkylamines –> anti-arrhythmic
- benzothiazepines –> Both
K+ and RMP
RMP is dominated by ionic species, greatest permeability to K+ across membrane
Tetramer is important, enables channels to heteromultimerise, allowing diversity
K.Ca
sensitive to voltage and [Ca2+]
Ca2+-binding domain to C-terminal domain
SK.Ca and IK.Ca
voltage insensitive
activated by low [Ca2+], bind Ca2+ indirectly via calmodulin
function is AP repolarisation
K.Ir
2 TM domains equivalent to S5-P-S6
several subfamilies
blocked by Mg2+
stabilise RMP near to Ek
strong rectifiers close upon strong depolarisation of Vm
Weak rectifiers pass more outward current at depolarised Vm