Ion channel receptor pharmacology & local anaesthesia W13

Question 1

What does the phosholipid bilayer do?

Answer 1

Semi permeable barrier seperating cytosol and interstial fluid (intracellular and extracelluar compartments)

Question 2

What is the main component of the cell membrane and how does this effect movement across the membrane?

Answer 2

Composed of mainly lipids.
= electrically charged particles cant pass

Question 3

Pores in the membrane (transmembrane proteins) are selectivly permeable, allowing some ions to pass but not others. What determines what can pass through?

Answer 3

Only ions of appropriate size and charge can pass through the pore. The amino acids lining the pore lumen determine selectivity.

Question 4

Pores that are open all the time are called ____, (give example), others that open when stimulated are called _____.

Answer 4

Leak channels Ex. Na leak channel
Gated ion channels

Question 5

What are the main types of ion channels

Answer 5

Voltage-gated ion channels
Ligand-gated ion channels
Mechanically-gated channels

Question 6

What is a gap junction - give an example

Answer 6

Pores that allow direct communication between adjacent cells. Connexon proteins form the pore
Ex. Cardiac myocytes connected via Gap junction (= electical coupling)

Question 7

What is the difference between leak channels and gap junctions?

Answer 7

Leak channels are selective for specific ions, Gap junctions are pores that are mostly non-selective and allow the movement of many small things.

Question 8

How might one get better control over ion movement across membranes?

Answer 8

Introduce a gate (or valve), More selective pumps, Selectivity filter in the pores, Change the ion concentrations on either side of the membrane.

Question 9

What are aqaua porins

Answer 9

Pores allowing H2O to pass through- e.g. ADH inserts them for water reabsorption.

Question 10

What types of stimuli operate the gates?

Answer 10

Mechanical, voltage, chemical, ligand

Question 11

Name the following channels

Answer 11

Question 12

Which of the following is an example of a ligand-gated channel?

Nicotinic channel
voltage-gate K+channel
Na+/ K+ATPase
Leak channel
Gap junction

Answer 12

Nicotinic channel (Ach = ligand)

Question 13

Which of the following is an example of a voltage-gated channel?

Nicotinic channel
voltage-gate K+channel
Na+/ K+ATPase
Leak channel
Gap junction

Answer 13

voltage-gate K+channel

Question 14

How do intra-oral lasers cause analgesia? Where do they act?

Answer 14

Na+/K+ ATPase pump
Prevent the return to resting membrane potential

Question 15

Describe the chemical structure of L.A

3 components

Answer 15

Aromatic ring linked by ester or amide bond to tertiary amine

Question 16

Where do local anaesthetics act?

Answer 16

voltage-gate Na+channel

Question 17

Where on the channel do LA act?

Answer 17

Block pore from the inside - cytosolic side = prevent voltage dependent initiation/propagation of AP

Question 18

The terminal amine can exist in 2 states…?

Answer 18

Tertiary= 3 bond, lipid soluble
Quaternary = 4 bond, water soluble

Question 19

Which state has a weak vs strong channel blocking activity and why?

Answer 19

Tertiary - lipid soluble, unionised = can cross membrane easily but weak blocking effect.
Quaternary - water soluble, ionised = block more strongly.

Question 20

Describe the steps from injection to onset of L.A

Answer 20

1. Quaternary (ionised) form injected
2. Changes to Tertiary form at certain pH (7.4)
3. Tertiary form (unionised) crosses the membrane
4. Tertiary -> quaternary in the cytosol = blocks Na+ channels = Onset

Question 21

How can inflammation disrupt the onset of L.A?

Answer 21

inflammation/infection -> acidic environment
= favours quaternary (ionised form)
= can’t cross membrane = no onset

Question 22

L.A is most effective on ____ nerve fibres.

Answer 22

Non-myelinated
- Mostly post-ganglionic

Question 23

Voltage gates Na+ channels can exist in 3 states…

Answer 23

1. Open
2. Closed
3. Inactive

Question 24

Explain the two componets of the use-dependent block of L.A’s

Answer 24

1. L.A’s binds mostly to inactivate state Na+ channels = reduced number of channels avaiable for opening = prolonged refractory period
2. Following noxious (pain) stimulus, nerve fires an AP = Na+ channels to cycle between open and inactivated state (both bond more L.A than in the closed state) = pain transmission effectively blocked > sensory stimuli

Question 25

Which part of the L.A chemical structure provides resistance to metabolic hydolysis in the plasma or tissues?

Answer 25

Amide/Ester bond