1. Chapter 3
The Neuronal Membrane
at Rest

2. Introduction
Action potential in the nervous system
Action potential vs. resting potential

3. The Cast of Chemicals Cytosolic and Extracellular Fluid Water
Key ingredient in
intracellular and extracellular fluid
Key feature – water is a polar solvent

4. Cytosolic and Extracellular Fluid (Cont’d)
Ions: Atoms or molecules with a net electrical charge
Cations: positive charge
Anions: negative charge
Spheres of hydration

5. The Phospholipid Membrane
Hydrophilic
Dissolve in water due to uneven electrical charge (e.g., salt)
Hydrophobic
Does not dissolve in water due to even electrical charge (e.g., oil)
Lipids are hydrophobic
Contribute to resting and action potentials

6. The Phospholipid Bilayer

7. Protein
Molecules
Enzymes
Cytoskeletal elements
Receptors
Special transmembrane proteins
Control resting and action potentials

8. Protein
Structure
Amino acids
Alpha carbon and R groups

9. Protein
Structure (Cont’d)
Peptide bonds and polypeptides

10. Protein
Structure (Cont’d)
Four levels of protein structure
Primary, Secondary, Tertiary, Quaternary

11. Protein
Channel Proteins
Polar R groups and nonpolar R groups
Ion selectivity and gating

12. Protein
Ion Pumps
Formed by membrane spanning proteins
Uses energy from ATP breakdown
Neuronal signaling

13. The Movement of Ions
Diffusion
Dissolved ions distribute evenly
Ions flow down concentration gradient when:
Channels permeable to specific ions
Concentration gradient across the membrane

14. Electricity
Electrical current influences ion movement
Electrical conductance (g) and resistance (R); R = 1/g
Electrical potential (voltage)

15. The Chemicals Involved in the Conduction of Electricity
Electrical current flow across a membrane
Ohm’s law I = gV

16. The Ionic Basis of The Resting Membrane Potential
Membrane potential: Voltage across the neuronal membrane

17. Equilibrium Potential (Eion)
No net movement of ions when separated by a phospholipid membrane
Equilibrium reached when K+ channels inserted into the phospholipid bilayer
Electrical potential difference that exactly balances ionic concentration gradient

18. Equilibrium Potentials
Four important points
Large changes in Vm
Minuscule changes in ionic concentrations
Net difference in electrical charge
Inside and outside membrane surface
Rate of movement of ions across membrane
Proportional Vm – Eion
Concentration difference known: Equilibrium potential can be calculated

19. Equilibrium Potential
Inside positively charged relative to outside

20. Voltmeter
Plasma
membrane
Ground electrode
outside cell
Microelectrode
inside cell
Axon
Neuron

21. K+ A– Na+ Cl– Cell exterior Na+ 15 mM Na+ Cell interior 150 mM ion Na+
Diffusion us
Na+–K+
pump
Diff
-70 mV
Cl–
10 mM
Na+
Na+
Na+
150 mM A–
100 mM K+
Na+ A–
0.2 mM
Na+
Plasma
membrane K+
5 mM K+
Cl–
120 mM K+
Cell
interior
Cell exterior K+ K+

22. Depolarizing stimulus
Hyperpolarizing stimulus
+50
+50
Inside
positive
Inside
negative
Membrane potential (voltage, mV)
Depolarization
–50
Membrane potential (voltage, mV)
–50
Resting
potential
–70
–70
Resting
potential
Hyper-
polarization
–100
–100 1 2 3 4 5 6 7 1 2 3 4 5 6 7
Time (ms)
Time (ms)
(a)
(b)

23. Depolarized region
Stimulus
Plasma
membrane
(a)
Depolarization
(b)
Spread of depolarization

24. Active area
(site of initial
depolarization)
Membrane potential (mV) – 70
Resting potential
Distance (a few mm)

25. Outside
cell
Na+
Outside
cell
Na+
Inside
cell
Inside
cell K+ K+ 2
Depolarizing phase: Na+
channels open
Repolarizing phase: Na+
channels inactivating, K+
channels open
Action potential
+30 3
Relative membrane
permeability 2
Membrane potential (mV)
PNa PK
Threshold
–55 1 1 4
–70 1 2 3 4
Time (ms)
Outside cell
Sodium
channel
Potassium
channel
Outside
cell
Na+
Na+
Inside
cell
Activation
gates K+
Inside
cell K+
Inactivation gate 4
Hyperpolarization: K+
channels remain open;
Na+ channels resetting 1
Resting state: All gated Na+
and K+ channels closed
(Na+ activation gates closed;
inactivation gates open)

26. Voltage
at 2 ms
+30
Membrane potential (mV))
Voltage
at 0 ms
Voltage
at 4 ms
–70
(a) Time = 0 ms
(b) Time = 2 ms
(c) Time = 4 ms
Resting potential
Peak of action potential
Hyperpolarization

27. Action
potentials
+30
Membrane potential (mV) – 70
Stimulus
amplitude
Threshold
Voltage
Time (ms)

28. Absolute refractory
period
Relative refractory
period
Depolarization
(Na+ enters)
+30
Repolarization
(K+ leaves)
Membrane potential (mV)
After-hyperpolarization
–70
Stimulus 1 2 3 4 5
Time (ms)

29. Equilibrium Potentials (Cont’d)
The Nernst Equation
Calculates the exact value of the equilibrium potential for each ion in mV
Takes into consideration:
Charge of the ion
Temperature
Ratio of the external and internal ion concentrations

30. The Distribution of Ions Across The Membrane
K+ more concentrated on inside, Na+ and Ca2+ more concentrated outside

31. The sodium-potassium pump
Enzyme - breaks down ATP when Na present
Calcium pump: Actively transports Ca2+ out of cytosol

32. Relative Ion Permeabilities of the Membrane at Rest
Neurons permeable to more than one type of ion
Membrane permeability determines membrane potential
Goldman equation
Takes into account permeability of membrane to different ions
Selective permeability of potassium channels - key determinant in resting membrane potential
Many types of Potassium Channel
Lily & Yuh Nung Jan—amino acid sequences; Family of K+ channels
e.g., Shaker Potassium Channel

33. Seymour Benzer – research leader in studies of Shaker Flies
Seymour Benzer – research leader in studies of Shaker Flies. In the 1970s, his lab was able to associate this mutant’s behavior to a gene that affects potassium channel development.

35. Relative Ion Permeabilities of the Membrane at Rest
K+ channels: 4 subunits
Channel selectively permeable to K+ ions
MacKinnon—2003 Nobel Prize
Mutations of specific K+ channels; Inherited neurological disorders

37. Relative Ion Permeabilities of the Membrane at Rest
Resting membrane potential is close to EK because it is mostly permeable to K+
Membrane potential sensitive to extracellular K+
Increased extracellular K+ depolarizes membrane potential

38. Relative Ion Permeabilities of the Membrane at Rest
Regulating the External Potassium Concentration
Blood-Brain barrier
Potassium spatial buffering

39. Concluding Remarks
Activity of the sodium-potassium pump
Large K+ concentration gradient
Electrical potential difference across the membrane
Similar to a battery
Potassium channels
Contribute to resting potential
Roles of ion pumps