L1, Intro to ion channels Flashcards
1
Q
Key types of biological membranes:
A
- Plasma membrane
- Vacuoles
- Mitochondria
- Chloroplasts
- Endoplasmic reticulum
- sarcoplasmic reticulum
- lysosomes
2
Q
Why is membrane transport important? (6 key areas)
A
- Osmoregulation and turgor control
- Nutrient acquisition
- Waste excretion
- Compartmentalisation of metabolism
- Energy transduction
- Signal transduction
3
Q
Characteristics of primary pumps:
A
- Use primary source of energy (usually ATP) to pump ions against electrochemical gradients
- Primary active transport
- Usually pump hydrogen or sodium cations
- Pumps are ‘electrogenic’; establishing electrochemical gradients for ‘driver’ ions
4
Q
Characteristics of ‘carriers’ (including main classes)
A
- Energised by ‘driver’ ion e/c gradients -> secondary active transport
- Symporters/co-transporters
- Antiporters/counter-transporters
- Facilitators/uniporters (can’t be energised; allow facilitated diffusion passively down e/c gradients of chemical gradients
5
Q
Characteristics of channels:
A
- Always passive transport down e/c gradients
- Usually highly regulated with defined open and shut kinetics (referred to as ‘gating’)
- Usually selective for specific ions (e.g. Calcium channels)
6
Q
How many ion channels are encoded by the human genome?
A
Approximately 500
7
Q
How do ion channels compare as drug targets?
A
- Second biggest group of drug targets after GPCRs
- 18% of small-molecule drugs
8
Q
4 Key properties of ion channels:
A
- Permeation
- Selectivity
- Gating
- Modulating
9
Q
How may a channel distinguish between cations and anions?- Include examples
A
- Cations: Rings of negatively charged residues in pore (e.g. AChR)
- Anions: Ring of positively charged residues and neutral hydrophobic residues (e.g. glycine receptor)
10
Q
Common method for complex selectivity in channels:
A
- Precise architecture and distances between charges allow the pore to select between cations
- e.g. K+ selectivity is determined by hydration energies (too great for Na+)
11
Q
What factors influence frequency of opening/closing in gating?
A
- Changes in membrane voltage
- Binding of I-C or E-C ligands; usually binding opens (e.g. AChR) but can also cause closure (K-ATP channels)
- Mechanical stress
- Changes in temperature
12
Q
+ Inactivation with Na+ example
A
- Flow of ions is blocked by a mechanism other than the closing of the channel
- Typically occurs when cell membrane depolarises
- In sodium channels, inactivation appears to be result of helices III-VI; hinged lid mechanism
- Ensuring unidirectional propagation of signal (e.g. in APs)
13
Q
How may a channel be modulated:
A
- Occurs in nearly all channels
- Wide variety of substances; Calcium, H+, ATP, fatty acids, phosphorylation, G-proteins
- Influencing gating following activation
14
Q
Potential functions of accessory proteins:
A
- Specifying their location and abundance of ion channel (e.g. Rapsyn clusters at AChR at excitatory synapses)
- Modulate ion channel gating (SUR subunit of K-ATP channels has a key role in hydrolysing ATP to stimulate channel opening) -> fine tune sensitivity to physiological and pharmacological agents (SUR is the target of drugs used to treat diabetes)
15
Q
3 methods for studying ion channels:
A
- Electrophysiology (properties and activity)
- Cloning and determining primary sequence (useful for finding homologues and building evolutionary profiles)
- Topology (identification of structure and function)
