SN5 - cellular mechanisms for ion homeostasis

Question 1

What are the cellular mechanisms for ion homeostasis

Answer 1

Ion channels
Pumps
Transporter

Question 2

Discuss the action of digitalics on cellular mechanisms of ion homeostasis

Answer 2

From the Digitalis purpurea plant:
Blocks sodium-potassiumATPase pump - it is an ANTIPORTER (sodium out, potassium in). By blocking it causes intracellular sodium to increase, affecting function of exchanger, sodium will the move out as the gradient increases in exchange for CALCIUM. Thus increase in intracellular calcium thus increasing contradiction in cardiomyocyte.

Question 3

3 kinds of ion channel

Answer 3

Voltage gated
ligand gated
Stretch activated

Question 4

Discuss the membrane potential regulation of a potassium channel

Answer 4

6 alpha helix TMD:
Voltage sensor on TM4
Selectivity filter H5
Inactivation gate - globular domain at N terminal on potassium channel
FOUR copies of this protein form a ring around the channel pore

Question 5

Sodium channel membrane potential regulation discuss

Answer 5

Only one chanel (one long connected 4 motif containing protein) - it has a LOOP which closes the channel on the inside

Question 6

Tetrodotoxin mechanism of action

Answer 6

Sodium channel BLOCKER

Question 7

Name 3 therapeutic sodium channel blockers. What is the blockage dependent on. How does the blockage work exactly?
Does it bind?

Answer 7

1. local anaesthetics (can still feel pressure)
2. antiepiletics
3. antiarthmics
   The blockage is voltage / use dependent. It blocks by entering the channel, the more you open the channel the more drug gets in and this is how you block. It binds electrostatic ally

Question 8

Calcium channel drugs:

Discuss the type of calcium channels and their locations

Answer 8

LVA: T - muscle, neurons, endocrine
HVA:
L - heart, muscle, neurons, endocrine cells
N: neurons, endocrine
P/Q - neurons

Question 9

What happens if you block L type channels and name drugs that do this

Answer 9

Blocking L type (HVA Calcium channel) will block heart contractions 
Phenylalkyl amines (verapamil, benzothiazepines) = antiangina, antihypertensive, antiarrythmics
Dihydropyridines (nifedipine) = work on blood vessels = antihypertensive, antianginal

Question 10

Name 2 functions that G protein coupled receptors (GPCR) have in the ANS

Answer 10

Controls:

1. enzymes
2. ion channels

Question 11

Discuss the cascade of a Beta 1 adrenergic receptor in the heart

Answer 11

NE from sympathetic nerve, binds, activates receptor, coupled to Gs protein, production of cAMP activates PKA, phosphorylates protein, one of them being a calcium channel, once phosphorylated it opens = more calcium opens = sympathetic mechanism for increasing contractility.

Question 12

Discuss the parasympathetic stimulation in the heart - cascade.

Does it have a second messenger system?

Answer 12

Ach –> Muscarinic receptor (M2) which is Gi protein coupled, activates the G protein and it dissociates into 2 components (alpha) and (beta gamma). The beta-gamma interacts with potassium channel and opens it, allowing potassium to flow out, hyper polarisation = inhibition
NO SECOND MESSENGER - direct interaction of G protein and receptor.