Lizzy - ion channel diversity Flashcards
difference between neuron and heart action potentials.
graphs.
draw out in notes
main types of ion channels?
ion gated and ligand gated.
others that dont fit, ie aquaporins
what are the types of voltage gated Ca channels?
L type:
- high voltage activated
- DHP sensitive
High voltage activated
DHP insensitive
T type:
- low voltage activated
what were ion channels classified due to at first?
Electrophysiology – ion selectivity, voltage-dependence, current kinetics
Pharmacology – agonist/antagonist activity of specific drugs
Modulation by regulatory molecules – Ca2+, Gβγ, ATP
Structure – topology of pore-forming subunits, auxiliary subunits, amino acid sequence
describe the voltage gated K channels.
- most primitive
- 6 TMD
- intracellular N and C terminus
- voltage sensor on S4 coupled to the pore region to allow opening.
- pore region between S5 and S6, membrane dipping/P loop. contains selectivity filter
- for a functional channel we need 4x a subunits, the pore loops form the lining of the channel.
- B subunits enhances cell surface expression and modulate channel gating (inactivation)
describe TM B subunits in Nav channels.
- short intracellular tail and long extracellular head.
- different to Kav B unit.
- modulates channel gating
- can function autonomously independent of the pore forming part of channel, has role as cell adhesion molecules.
- regulate cell surface expression.
describe B subunits in Kav channels
- B subunits enhances cell surface expression and modulate channel gating (inactivation)
- 4 TMD
- linked to voltage sensor?
describe the Ca voltage channels
- 1 B and 1 a2delta
- B subunit is an intracellular protein
- a2delta transmembrane glycoproteins
- gamma subunits.
only gamma1 associated with Cav, ignore it basically.
describe the voltage sensing region
- S4
- positively charged arginine or lysine every 3/4 residues within S4 of voltage gated channels.
- when a V gated channel opens charged amino acids move through membrane electric field, coupling electrical work to the process of opening.
slide about ball and chain?
no idea m8
N-type – N-terminal amino acids (~20) act as “ball” to plug channel pore.
Some βs fulfil similar function.
C-type – Constriction of outer mouth of pore
describe Na voltage gated channels and their roles.
Most recent voltage-gated channel in evolutionary terms
Essential role in initiation &
propagation of APs in excitable cells.
Important targets for Local anaesthetics, anticonvulsants & antiarrhythmic agents
Development Nav-selective drugs for tmt of pain
what are the types of Nav currents?
TTx-s (Tetrodotoxin-sensitive)
Blocked by TTx in nM range (1-100 nM)
Rapid activation/inactivation
Low threshold of activation
E.g. skeletal muscle, nerve
rapid on rate and peak
open at smaller depolarisations
TTx-r (Tetrodotoxin-resistant)
Blocked by µM TTx (1-10 µM).
Slower activation/inactivation
Activate at more depolarised potentials
E.g. cardiac muscle, sensory neurons
slower, less amplitude
where do TTX/STX bind on an a subunit in a Na channel?
TMD1 on the extracellular loop between 5/6
? idk what this is for probs ignore it
describe where local anaesthetics bind?
S6 domain I, III & IV
S6 are critical for inactivation of the pore.
lock the channel into an inactivated state.
when do cav channels open?
when the cell membrane is depolarised.
