Lecture 3: Neuronal Signalling In The Context Of CNS Disorders Flashcards
1
Q
What are the 2 components of the driving force for transmembrane transport?
A
- Chemical Driving force - ions distributed on both sides
- Electrical Driving force - charge difference across the membrane
- Electrical gradient + Chemical gradient = Electrochemical gradient (generated by mechanisms of active transport)
2
Q
Which ions of K+, Ca2+, Cl-, Na+ concs are higher in the cell? And what is the definition of membrane potential?
A
- Only K+ higher in the cell. Rest are lower. Negative charge inside cell
- Membrane potential (VM) is a sum of equilibrium potentials of all contributing ions. It is the voltage difference across the plasma membrane
3
Q
What are the types of passive transmembrane transport?
A
- Simple Diffusion: free movement of ions/ molecules from high -> low conc. No carriers
- Facilitated Diffusion: Helped by transmembrane carriers and ion channels (integral transmembrane proteins forming pores for the ions). Release energy
4
Q
What are the types of active transmembrane transport?
A
- Primary active transport: Low-> high concs using ion pumps and using ATP. ATPase pumps
- Secondary active transport: uses free energy of the electrochemical gradient for 1 component to transport another against its chemical gradient. E.g Na+/Ca2+ exchanger (Uses energy of Na+ to exchange w: Ca2+)
5
Q
What are voltage gated ion channels?
A
- Transmembrane proteins that form ion channels that are activated by changes in the membrane potential
- Usually ion specific (Na+/K+/Ca2+)
- Open with a stimulus that causes depolarisation
6
Q
What are ligand gated ions channels?
A
- These ion channels or receptors are membrane proteins that open by binding of neurotransmitter, hormone or drug
- E.g nicotinic acetylcholine receptor
- Typically non-selective
7
Q
What are G-protein coupled receptors?
A
- Detect molecules outside the cell and activate internal signal transduction pathway (not ion channel or carrier)
8
Q
Explain the G-protein cycle with adrenaline
A
- Adrenaline binds to adrenoceptor which causes B-adrenoceptor/G-protein interaction
- GDP gets exchanged for GTP (on a subunit)
- Causes a-subunit to separate from the rest
- Free a subunit activates AC causes ATP to change to cAMP and PKA activation
- Unbinding of adrenaline -> GTP hydrolysis
9
Q
What are the different alpha subunits in G protein coupled receptors and what to they do?
A
- Gs - stimulates AC. ATP- cAMP - PKC
- Gi - inhibits AC
- Gq11 - allow hormones/neurotransmitters to activate Phospholipase C (PLC). Cleaves Pip2 into IP3 and DAG (stimulate Ca2+ release)
10
Q
What is depolarisation?
A
- When membrane potential Vm is less than -70mv. Charge difference is reduced between the inside and outside the cell.
- Results in increased influx of Na+ and/or Ca2+
- Increased neuronal excitability
11
Q
What is hyperpolarisation?
A
- When the membrane potential is more than -70mv. Increase in charge difference between inside and outside
- Results in increased efflux of K+ (leaks)
- Decreased neuronal excitability
12
Q
What is action potential?
A
- Is the change in voltage that occurs between the inside and outside of an excitable cell
- Neuron or muscle cell/fibre
- Spontaneously or as a result of stimulation
13
Q
What happens in Phase 0 & 4?
A
- Resting membrane potential and slow depolarisation (membrane is polarised)
- Voltage gated Na+ channels = closed, VG K+ = open
- HCN - hyperpolarization and cyclic nucleotide gated channels activate H.polzation permeable to Na+ (can do K+)
14
Q
What happens in phase 1 of depolarisation?
A
- Fast depolarisation
- Neurotransmitters interact w/ receptors causes depolarization and reaches threshold (-55mv)
- Fast Voltage Gated Na+ channels open - rapid influx. Causes AP and travels along neuron
- Slope = max rate of depol = vMAX
15
Q
What happens in phase 2 of depolarisation?
A
- Repolarisation
- Action potential reaches peak Na+ channels close and K+ channels open. Rapid Efflux
- It overshoots - hyperpolarized (refractory period) hard to fire again
