Membrane potentials

Question 1

What is the physicochemical properties of nerve cell membranes?

Answer 1

1. Lipid bilayer:
   - Lipid tails, hydrophilic heads
   - Cholesterol provides rigidity
2. Membrane proteins
   - Integral transmembrane proteins
   - Extrinsic/peripheral membrane proteins

Question 2

What is the function of a membrane?

Answer 2

• Provides cellular structure
• Fluidity of membrane/cell
• Physical barrier prevents free passage of
  substances:
  – Selectively permeable
  – Cell can maintain different mixtures of substances inside and outside

Question 3

What is the composition of charged solutes inside and outside the cell?

Answer 3

Question 4

What is the composition of uncharged solutes inside and outside the cell?

Answer 4

Question 5

Discuss the methods of transport across the cell membrane.

Answer 5

1. Diffusion: O2, CO2 & lipid-soluble molecules freely diffuse.
2. Protein-mediated membrane transport
3. Endocytosis: Phagocytosis & Pinocytosis
4. Exocytosis

Question 6

What is passive transport?

Answer 6

• Molecules for which the plasma membrane is permeable can diffuse across.
• Movement from a region of high electro-chemical potential to a region of lower electro-chemical potential.
• Aim: establish equilibrium between intracellular and extracellular concentration and charge.

Question 7

What is selective permeability?

Answer 7

• The ability to differentiate between different types of molecules and only allowing some molecules through while blocking others.
• e.g High permeability for K+ & Low permeability for Na+ and Cl.

Question 8

What are the types of gated ion channels?

Answer 8

• These are integral membrane proteins that contain a pore which allows the regulated flow of selected ions across the plasma membrane.
• 2 types:
  1. Ligand-gated: Ligand receptor site and ligand binding induces conformational change to
  open or close the channel.
  2. Voltage-gated: Voltage sensor in the ion channel protein. Changes in membrane potential induce a conformational change to open or close the channel.

Question 9

Give examples of drugs acting on voltage gated ion channels.

Answer 9

1. Local anaesthetics
   – Inhibit voltage-gated Na+ channels e.g. lidocaine
2. Antihypertensive agents
   – Voltage-gated Ca2+ channel blockers e.g. Nifedipine
3. Antiarrhythmic drugs
   – Inhibit voltage-gated K+ or Na+ channels

Question 10

What is active transport?

Answer 10

• Carrier-mediated transport that requires ATP.
• Only open to one side at a time.
• Can move substances against the electro-chemical gradient.
• Primary or secondary

Question 11

What is primary active transport in relation to Na+/ K+ ATPase pump?

Answer 11

Question 12

What is secondary active transport and give an example.

Answer 12

• Co-transporters (symport) of substances against their own gradients.
• E.g Sodium-glucose cotransporter (SGLT) mediates apical sodium and glucose transport across cell membranes.
  **Driven by active sodium extrusion by the basolateral sodium/potassium-ATPase.
• Exchange (anti-port) of solutes against their electro-chemical gradient e.g Na/Ca exchanger.
  **Also driven by Na/k ATPase.

Question 13

What is the solute composition of major ions across the membrane and why is it important?

Answer 13

Stable ion concentration and ion charge gradients are essential for normal physiology.

Question 14

What is the resting membrane potential?

Answer 14

• Difference in electrical charge across plasma membrane that maintains an electrostatically neutrality.
• Approx. -70 mV in a typical neuron (-60 to -100 mV)
• Inside of the membrane more negative than outside.

Question 15

How membrane potentials detected?

Answer 15

• By microelectrodes or potential sensitive indicators.

Question 16

What is the implication of RMP in ion flux?

Answer 16

• Charge gradient + concentration gradient =
  electrochemical gradient
• At equilibrium, the charge gradient balances the
  concentration gradient, and there is no net flow of ions across the membrane.

Question 17

What is an equilibrium potential and how is it calculated?

Answer 17

• The electrical potential difference across the cell membrane that exactly balances the concentration gradient for an ion.
• Calculated by Nernst equation.

Question 18

How is the resting membrane potential determined?

Answer 18

• K+ that leaks from the inside of the cell (highest conc.) to the outside (lowest) via leak K+ channels and generates a negative charge in the inside of the membrane vs the outside.
• If there is no net transport of K+, the electrical potential across the membrane at this equilibrium = Nernst equilibrium potential, which for K+ = -90 mV.
• But we must also consider Na+ where its concentration gradient drives it into the
  cell. The electrical gradient (more negative inside cell) also drives Na+ into the cell. This Na+ transport also reduces the membrane potential created by K+ alone.
• So RMP = -70mV inside the neuron.
• Other ions contribute to the RMP but to a lesser extent.

Question 19

What happens when ion channels open?

Answer 19

• Ions will move along their electrochemical gradients towards their equilibrium potential
• The membrane potential (MP) will change as a result.
• E.g Given RMP= -70mV. Opening K+ channels will move MP toward -90mV.
• Given ENa+ = +60 mV, opening Na+ channels in the membrane will move MP toward +60mV.
  **RMP is always close to the K+ equilibrium potential (EK+).

Question 20

Discuss excitable cells and their relation to MP.

Answer 20

• Excitable cells (e.g. neurons, cardiac cells) actively induce changes in their membrane potential.
• This is the basis for electrical excitability of nerve and muscle!
• Imbalance in excitation and inhibition can lead to disease (e.g. hyperexcitability in epilepsy

Question 21

What is the effect of changes in Na/k concentrations on the RMP?

Answer 21

• e.g Hyperkalaemia shifts RMP closer to action potential threshold. Cells become more excitable.
• High K+ used to induce seizures in neuronal cultures
• KCl injection is used as a form of capital punishment (arrhythmia/cardiac arrest)