BMS2002 - membrane transport and ion channels

Question 1

protein classes in the plasma membrane

Answer 1

transporters, linkers, receptors, enzymes

Question 2

types of membrane transporters

Answer 2

channel protein
carrier protein
pump

Question 3

passive transport

Answer 3

along concentration gradient
no ATP hydrolysis

Question 4

3 main types of passive transport

Answer 4

simple diffusion
osmosis
facilitated diffusion

Question 5

active transport

Answer 5

movement against concentration
energy expended - ATP

Question 6

2 main types of active transport

Answer 6

1. primary/direct - directly uses ATP
2. secondary/indirect - couples with another molecule moving along electrochemical gradient

Question 7

Na+/K+ ATPase

Answer 7

Na+ in cytoplasm binds pump
pump is phosphorylated by ATP
conformational change -> NA+ release
EC K+ binds pump -> dephosphorylation
pump returns to original conformation
K+ is released from the pump

Question 8

3 ways of gating ion channels

Answer 8

voltage-gated
ligand-gated
tension-gated

Question 9

flux

Answer 9

movement, occurs due to concentration across the membrane

Question 10

mammalian Vm

Answer 10

~55mV

Question 11

resting membrane potential maintained by….

Answer 11

sodium potassium pump

Question 12

equilibrium potential is when

Answer 12

ion flux in = ion flux out

Question 13

what to look for when investigating ion channel structure

Answer 13

• biochemical properties of specific aa side chains -> predict protein structures
• hydrophobic = transmembrane region
• polar/charged/hydrophobic = extramembrane, ligand binding

Question 14

experimental ways of investigating ion channel structure

Answer 14

X-ray crystallography - standard
Electron microscopy - emerging

Question 15

characteristics of ion channels

Answer 15

• can be difficult to crystalise
• transmembrane
• large proteins
• multiple conformations
• multiple subunits
• dynamic and disordered
• not very stable

Question 16

ion channel structure

Answer 16

multiple alpha subunits - typical potassium channel has 4 = tetramer

Question 17

4 stages of an action potential

Answer 17

1. resting phase
2. depolarisation
3. repolarisation
4. hyperpolarisation (Refractory)

Question 18

absolute refractory period

Answer 18

• membrane cannot generate another action potential
• sodium channels are inactivated

Question 19

relative refractory period

Answer 19

• membrane could generate another action potential if given a larger than normal stimulus
• VG sodium channels are recovered
• VG potassium channels are still open

Question 20

movement of action potential down an axon

Answer 20

travels via current loops
- nearby area becomes depolarised by the current AP to initate the next AP

Question 21

channelopathy

Answer 21

pathology or disease arising from ion channel dysfunction

Question 22

3 pain mechanisms

Answer 22

1. noiciceptive - temperature, acid, etc
2. inflammatory - immune
3. neuropathic - nervous

Question 23

pathway of noxiuos stimuli

Answer 23

noxious stimuli -> peripheral terminals of specific unmyelinated C-fibre and thinly myelinated Ad fibre -> spinal cord -> central pathways -> cortex -> pain is experienced

Question 24

options for neuropathic pain treatment

Answer 24

TCAs, anticonvulsants, Na+ channel blockers, NMDA receptor antagonists, opiods

Question 25

4 therapeutic strategies for pain

Answer 25

INHIBIT the ion channel that:
1. senses the stimuli/initiates the AP
2. propagates the AP
3. are involved in DRG neurotransmission
4. process stimuli centrally within the brain

Question 26

Primary Erthromelagia (PEM)

Answer 26

autdom mutation in SCN9A
- bilateral burning and redness in hands and feet
- attacks triggered by exersize / heat
mutation -> shift in hyperpolarizing direction -> reduced threshold -> increased excitability
-> increased symptom severity

Question 27

Paroxysmal extreme pain disorder

Answer 27

autdom mutation in SCN9A
- severe pain in rectal/ocular/mandibular areas
- triggered by chewing/heat
- mutation -> incomplete channel activation
- treated with carbamazepine

Question 28

Complete insensitivity to pain (CIP)

Answer 28

autres mutation in SCN9A
- loss of all pain sensation
- nonsense mutations -> truncated proteins
- often suffer major injuries as a result