Part 1 Flashcards
what are the three basic functional properties of ion channels?
- Conduct
- Select
- Gate
What are the therapeutic effects of ion channels?
Can be used to treat:
- Cardiac arrhythmia’s
- Epilespy
- Local anaesthetic
Why do we need ion channels?
Ions cannot pass through hydrophobic barriers/ ion channels provides a polar environment for the ions to pass across membranes.
Name a few specialised functions of ion channels
- Mediate the generation, transmission and conduction of electrical signals in the CNS
- Initiates muscle contraction
- Allows small molecules to pass through gap junctions
- Controls release of NT and Hormones
- Provides selective permeability (important for intracellular organelles
What are the five different types of ion channels?
- Channels activated by NT binding (non -selective cation) apart from GABA/Serotonin - chloride
- Channels activated by ATP and Purine nucleotide binding (Non selective cation)
- Voltage gated channels (Non selective cation)
- CLC CL family channels (permeant channels) (selective - chloride)
- Gap junction channels (the only non gated ion channels) (non selective)
How do ion channels achieve their specificity?
They have ion-protein interactions
What are the stochastic properties of ion channels?
Single channel opening is an all or nothing in amplitude. Stochastic properties may alter the probability of ion channel opening and the duration of which it remains open.
What are the different types of ion gating?
- Voltage gating
- Ligand gating
- Second messenger gating (i.e via phosphorylation)
- mechanical force gating
- Temperature gating
What does an orthosteric ligands do and how do they act?
They act via an endogenous ligand
- Replicate the efficacy of endogenous ligand (agonist)
- Prevent binding of lingand with no intrinsic efficacy (Antagonist)
What do positive and negative allosteric modulators do?
Positive - Enhances/amplifies endogenous agonist effect and also enhances binding affinity
Negative - Reduces endogenous antagonist effect.
What do non competitive antagonists do?
They prevent channels opening even when agonist is bound e.g channel blockers.
How are channels modified?
By tyrosine/threonine/seronine phosphorylation, this is done by
- Altering the membrane expression
- Altering the opening probability
- Altering the ligand binding
Name the different types of ligand gated NT in the brain and their function
- Glutamate - Excitatory NT in the brain
- GABA - Inhibitory NT in the brain
- Acetylcholine - NT found in peripheral motor nervous system
Give an example of a ligand gated channel
Nicotinic Acetylcholine receptor - it is pentameric and has four subunits/ its opening is has an allosteric effect. /channel remains open while the ligand bound so rapid clearance of synapse is important.
How do voltage gated ion channel work and what is their role?
Their role is to generate an action potential and they open when the membrane of the channel has depolarised. They are very selective and only use Ca, Na and K channels.
Describe the events of the cardiac action potential and state the resting potential
Phase 0 - Depolarisation, Rapid influx of Na
Phase 1 - Partial repolaristaion, Na ions inactivated
Phase 2 - Plateau, Ca ions flow inwards and K ions flow outwards (voltage gated ion channel open)
Phase 3 - Repolarisation, Ca ions inactivated and K ions slowly flow outwards
Phase 4 - Pacemaker action potential is maintained with NA/KATpase and K leak channels (resting potential is -90mv
Describe the different classes of anti-arrhythmic drugs and what phases of the cardiac action potential do they inhibit
Class 1 - Na channels and it prevents depolarisation in phase 0
Class 3 - K channels and it prevents repolarisation in phase 3
Class 4 - Ca channels and it prevents plateau in phase 2
What is epilepsy?
seizures with episodic of high frequency discharge by groups of neurons.
Describe how epilepsy can be detected and what causes the discharge by group of neurons?
The discharge by groups of neurons is caused by ligand gate or votage gated ion channels
It can be detected using an EEG
Area of the brain involved can be used to treat symptoms
What are the different types of seizures?
Partial seizures - tend to be localised
Generalised seizures - can be grand mal , petit mal
What are the different anti-epileptic therapies available ?
- Inhibit excitable volatage gated na channels
- Enhance GABA mediated synaptic inhibition
- Inhibit T cell type ca channels
What are local anaesthetics?
They are weak bases with ester linked aromatic groups.
How do local anaesthetics work?
They are voltage gated dependent Na channels and prevent action potential propogation.
What happens in resting and activated state in local anaesthetic?
Resting - Closed state / normal resting potential
Activated - Open state/ prefers depolarisation
