W5L2

Question 1

Common electrical units used

Answer 1

1. Potential (V)
   - Unit: Volt (V)
   - Typical range (electrophysiology): mV (10^-3 V)
2. Current (I)
   - Unit: Ampere (A)
   - Typical range (electrophysiology): nA (10-9 A), pA (10-12 A)
3. Resistance (R)
   - Unit: Ohms
   - Typical range (electrophysiology): M (10^6 ), G (10^9 )
4. Conductance (G)
   - Unit: Siemens (S)
   - Typical range (electrophysiology): nS (10-9 S), pS (10-12 S)

Question 2

Electrical voltage & current

Answer 2

Current = movement of charges

Direction of current = movement of positive charges from high to low electrical potential (voltage)

Height = electric potential V
Ball rolling down hill = current I

Question 3

Electric currents in excitable cells

Answer 3

In biological tissues, electrical activities are carried by ions (not electrons as in metals)

Ions = cations (+ ions) & anions (- ions)

Cations: Na+, K+, Ca2+, Mg2+

Anions: Cl-, HCO3-

Question 4

Ohm’s Law

Answer 4

V = IR

G = conductance = 1/R

I = GV

Question 5

Brain, neurons & channels

Answer 5

Neuron discovery (cajal, 1900s)
- unipolar, pseudounipolar, bipolar, multipolar

All neurons
- have resting membrane potential
- can fire AP; are excitable cells

Single channel recording in muscle cells done by Sakmann and Neher in 1970s

Question 6

Membrane and ion channels

Answer 6

Membrane
- phospholipid bilayer of 5 nm thick
- ions need to go through protein ion channels to cross the membrane

Important ions
- High outside cell
– Na+, Ca2+, Cl-
- High inside cell
– K+

Question 7

Ion channel

Answer 7

Has
- selectivity filter for molecule
- gate, controlled by the sensor of the channel

Ion channels are proteins that span the cell membrane to form pores, allowing ions to traverse the generally impermeable lipid bilayer.
- conduct ions
- selective
- open and close
- sensor

Question 8

Gating of channels

Answer 8

1. electrical (voltage-gated ion channels)
   - e.g. many Na+ channels, L- and T-type Ca2+ channels
   - for APs
2. chemical (ligand-gated ion channels)
   - nAChR, AMPAR, NMDAR & GABAAR
3. mechanical (mechanically gated ion channels)
   - physical separation

Subtle changes in conformation underlie opening of channel

Question 9

Voltage gating: Na+ channel activation

Answer 9

At rest, gate is closed

Then, if depolarization, it drives the sensor. Voltage sensor ‘moves’, so the gate opens and Na+ can go through the channel

Question 10

Major ions passing ion channels

Answer 10

1. Cations
   - Na+, K+ and Ca2+
   - Others: H+, Mg2+
2. Anions
   - Cl-, HCO3-

Physical properties
- Size, Charge, Hydration, Mobility: velocity [microns/s] in a unit electric field [V/cm]

Question 11

Hydration of ions

Answer 11

Water acts as a dipole to stabilize ions

1. Potassium
   - Size (radius) = 1.33 angstroms
   - Charge +1
   - Hydration # = 2.9
2. Sodium
   - Size (radius) = 0.95 angstroms
   - Charge +1
   - Hydration # = 4.5

Question 12

Physical properties of Na+, K+ and Cl-

Answer 12

Hydration depends on charge and size (OR charge density: amount of charge per unit volume)

Hydration number determines ionic mobility in water

1. Na+
   - atomic number 23
   - Crystal radius = 0.95 angstroms (1 angstrom = 0.1 nm)
   - hydration # = 4.5
   - Mobility = 5.2 (micrometers/sec)/(V/cm)
   - sodium moves slower than other ions bc it has more water with it
2. K+
   - atomic number 39
   - Crystal radius = 1.33 angstroms
   - hydration # = 2.9
   - Mobility = 7.6 (micrometers/sec)/(V/cm)
3. Cl-
   - atomic number 35.5
   - Crystal radius = 1.81 angstroms
   - hydration # = 2.9
   - Mobility = 7.9 (micrometers/sec)/(V/cm)

Question 13

Components of ion channels

Answer 13

Structure-function details of channels are becoming apparent from crystallographic and molecular biology studies

Components for the selectivity filter to work in potassium channel
1. i.e. Negative charge to repel anions away from the channel pore opening but will attract cations to the entrance
- i.e. glutamate
- potassium and sodium both carry water and enter the cell

2. Selectivity filter
   - rigid, not elastic, thin

ion channels also contain vestibule
- ion contains water in vestibule
- ion does not contain water in selectivity filter

Question 14

Hydration of ions & selectivity filter

Answer 14

Water acts as a dipole to stabilize ions

Carbonyl oxygens on peptide chain in the region of the selectivity filter replace water and stabilize each ion as it passes through the pore

Question 15

Number of subunits or domainsin an ion channel

Answer 15

4 subunits
- voltage-gated ion channel

5 subunits
- transmitter-gated ion channel (ligand-gated)

6 subunits
- gap junction hemichannels

Question 16

Oligomerization of subunits

Answer 16

1. Homo-oligomeric (homomeric)
2. Hetero-oligomeric (heteromeric)

Homo = same (subunit)

Hetero = different (subunits)

Oligo = more than one, e.g., dimer, trimer, tetramer