Physiological Mechanisms of Neuronal Potentials

Question 1

Outline key features of excitable cells.

Answer 1

Excitable cells are cells that have the ability to generate an action potential.

They are polarise: have a voltage across their membrane (generating or changing this membrane potential involves moving charged ions across their cell membrane).

The cytosol of excitable cells are separate from the extracellular solution by the existence of a phospholipid bilayer.

Question 2

Outline key features of passive diffusion.

Answer 2

Passive diffusion is when substances move down a concentration gradient (no energy is needed).

1. Simple diffusion - cell membrane is non-polar (in the layer of hydrophobic phospholipid tails), so only non-polar substances can move across the cell membrane by passive diffusion.
2. Facilitated diffusion:
   a. Carrier mediated - substances are bound by proteins and released inside the cell
   b. Ion channel mediated - ions diffuse into the cell through selective ion channels

Question 3

Outline key features of active transport.

Answer 3

Active transport is the transport of substances up a concentration gradient (requires energy).
1) Primary active transporters - using energy pumps move ion against their concentration gradient
2) Secondary active transporters - active transport of a substance up its concentration gradient by using the energy of a substance moving down its concentration gradient.

Question 4

What are ion channels and what is their structure?

Answer 4

Ion channels are facilitated diffusion proteins that traverse the membranes of all excitable cells. By controlling gating of these selective ion pores, cells are able to produce and transduce electrical signals.

Their structure:
a) Selectivity region at the superficial end of the pore –> act as a filter
b) Gate at the deep end of the pore –> opens and closes the channel in response to certain stimuli (ex. voltage, ligands)

Question 5

What is the sodium pump?

Answer 5

Also known as the Na+/K+ ATPase or Na+/K+ pump.
Uses energy to establish Na+ and K+ concentration gradients.
It directly uses energy from ATP (converting one molecule of ATP to ADP and an inorganic phosphate) to move 3 Na+ out of the cell and move 2 K+ into the cell.
It can be blocked by ouabain and cardiac glycosides.

Question 6

Which factors determine movement of an ion across a membrane?

Answer 6

1. The ion must be allowed to permeate the membrane via an ion channel.
2. There must be a force to allow the ion to move by passive diffusion through the ion channel
   a. Concentration gradient (chemical force)
   i. Efflux: inside –> outside
   ii. Influx: outside –> inside
   b. Influence from the electrical potential across a cell membrane (electrical force)
   i. Oppositely charged particles attract
   ii. Like charged particles repel

Question 7

What is the process of resting membrane potential generation in a real nerve cell?

Answer 7

1. Na+/K+ ATPase establish concentration gradients for K+ (high inside, low outside) and Na+ (high outside, low inside)
2. Na+ influx and K+ efflux would occur if transport proteins were available to facilitate this
3. Ion channels selective for K+ are opened
4. Selective efflux of K+ down its concentration gradient causes an excess of negative charge inside the cell, resulting in membrane potential
5. The negative membrane potential opposes the efflux of K+, apposing the action of the chemical force –> an electrochemical equilibrium develops (no net flux of ions)
6. This is the Nernst potential (equilibrium potential)

Question 8

What is the Nernst potential?

Answer 8

Aka the equilibrium potential - the membrane potential at which the electrical and chemical driving forces for ion flux across the membrane are exactly equal.

Question 9

What is the impact of high resting membrane permeability to K+?

Answer 9

High resting membrane permeability to K+ means the membrane is very sensitive to changes in K+ concentrations.
* Increase in extracellular (K+) by just a few mM –> depolarisation because membrane potential is primarily dependant on K+
- Hyperkalaemia –> muscle twitching, irregular cardiac rhythms
- Ischaemia –> elevated K+ and depolarisation contributes to ischemic cascade

Question 10

Which 2 mechanisms maintain K+ ion homeostasis?

Answer 10

• Spatial buffering
• astrocytes have an even higher K+ permeability
• ‘soak up’ and buffer K+
• K+ moved from active –> quiescent areas
• Blood brain barrier: brain is protected from peripheral changes