BIOSCI 107: Introduction to Neurons - The Resting Membrane Potential

Neuroscience

• A scientific discipline concerned with the function and structure of the nervous system.

• Nervous system = CNS (central nervous system) + PNS (peripheral nervous system)

• Cells = neurons + glia

The Challenge in Neuroscience

• To prevent and treat neurological and psychiatric disorders.

• Examples:

  • Alzheimer’s disease

  • Motoneuron disease

  • Parkinson’s disease

  • Autism

Overall Learning Objectives for whole topic

By the end of this module, you should be able to:

1. Describe and recognize the structure of a neuron.

2. Explain and discuss how the resting membrane potential is generated.

3. Explain and discuss how action potentials are generated and transmitted.

4. Explain and discuss mechanisms and features of synaptic communication.

Learning Objectives

1. Draw a neuron and label its basic structural features.

2. Explain the basis of the resting membrane potential (RMP).

3. Calculate equilibrium potentials for $K^+$ and $Na^+$ using the Nernst equation.

4. Use the Goldman equation to calculate the RMP

5. Explain the importance of Na/K ATPase in maintaining concentration gradients for Na+ and K+

Neurons

• Neurons (or nerve cells) are the principal building blocks and instruments of communication in the brain.

• Dendrite function is to receive electrical input

• Cell body passively conducts electrical signals

• Axon initial segment will initiate action potential

• Axons function is to propagate action potentials

• Axon terminal will release chemical signals

  • Communication through =

  • Electrical signals (dendrites, cell body, axon)

  • Chemical signals (synapses)

The Resting Membrane Potential (RMP)

• Experiment by A. Hodgkin and A. Huxley (1938) in squid giant axon

  • Nobel prize winners in Physiology and Medicine 1963

• In neurons and their processes, the cytosol has a potential that is minus 50 to minus 70mV lower (i.e., more negative) than the potential of the extracellular fluid.

RMP and Excitable Tissues

• Almost all cells in the body have a negative resting membrane potential.

• But only neurons and muscle fibers can suddenly respond with a transient change of this potential (i.e., an action potential) in response to a stimulus. Hence, they are ‘excitable tissues’.

Intracellular Potentials

• Measured today using:

  1. Microelectrode recording technique.

  2. Patch-clamp technique.

What Generates the RMP?

• Electrical potential difference (50 to 70 mV) across the cell membrane, which results from a separation of charge. There are more negative charges inside the cell in comparison to the extracellular fluid.

• Note: By convention, the potential outside the cell is defined as ‘zero’. Therefore, the intracellular potential is normally below zero (e.g., at -65mV).

• This can be due to:

  • Unequal concentrations of $K^+$ and $Na^+$ ions inside and outside neurons (approximately).

  • Unequal permeability of the cell membrane to ions

Ion Concentrations

• $[K^+]_o$ = 5mM

• $[Na^+]_o$ = 150mM

• $[K^+]_i$ = 100mM

• $[Na^+]_i$ = 15mM

How are the Concentration Gradients for $K^+$ and $Na^+$ Maintained?

• By the $Na^+$/$K^+$ pump.

• At a ratio of: 3 $Na^+$ out, 2 $K^+$ in.

Channels and Permeability

• Two main types of ion channels in neurons (i.e., channels which have selective permeability to ions):

  • i) Non-gated (‘leak’) channels

    • These are open at rest (‘on-off’ state), allows for diffusion of ions.

  • ii) Gated channels (voltage-gated, ligand-gated, or mechanically gated)

    • These are closed at rest.

• In the cell membrane of neurons, there are many leak $K^+$ channels, but very few leak $Na^+$ channels.

• Therefore, at rest: PK^+ / PNa+ ≈ 40/1 (where P is ‘membrane permeability’).

Concept of Equilibrium Potential & Nernst Equation

• The concept of the ‘equilibrium potential’ for one ion type is: an intracellular potential at which the net flow of ions is zero according to its electrochemical gradient.

Nernst Equation

• The equilibrium potential can be calculated for each ion by the ‘Nernst equation’:

  • E ion = 2.3 x RT/zF x log (ion)outside / (ion)inside

  • Simplified version = E ion = 61.5 mV x log (ion)outside / (ion)inside

• Calculate equilibrium potential for $K^+$ of this cell:

Equilibrium Potentials

• Equilibrium potentials can also be calculated for $Na^+$ (and other ions e.g. $Ca^{2+}$ and $Cl^-$

• $E_{Na^+} = +60 \text{mV}$

• Equilibrium potentials are a theoretical, conceptual value that indicates the chemical potential of an electron.

• The Nernst equation applies only to a situation when a cell membrane is permeable only to one ion! (i.e., has leak channels only for one specific ion). This is not the case for neurons.

• Note: Glia cells have leak channels only for $K^+$. Therefore, in glia cells, the RMP = $E_K = -80 \text{ mV}$

Key Rule

• Rule #1: The higher the permeability of the cell membrane to a particular ion, the more this ion shifts the RMP towards its own equilibrium potential.

• At rest in neurons, the membrane permeability is much higher to $K^+$ than to $Na^+$, therefore the RMP is closer to the equilibrium potential for K+ (Ek) than the equilibrium potential for Na+ (ENa)

• Thus, in comparison to glial cells, in neurons the RMP is less negative than $E_K$ (about -65 mV). This is due to a small contribution of leak $Na^+$ channels.

• Neurons have leak channels for $K^+$ and also leak channels for $Na^+$ which will affect RMP.

Concept of RMP & The Goldman Equation

• A way of calculating the value of the RMP taking into account both the concentration gradients AND the relative permeability of the resting cell membrane to $K^+$ and $Na^+$ ions.

• Vm = 61.5 mV x log Pk (K+)outside + PNa (Na+)outside / Pk (K+)inside + PNa (Na+)inside

• $[K^+]_o = 5 \text{mM}$

• $[Na^+]_o = 150 \text{mM}$

• $[K^+]_i = 100 \text{mM}$

• $[Na^+]_i = 15 \text{mM}$

• Remember:

  • $P_K = 40$

  • $P_{Na} = 1$

Application of Theory

• Imagine a sensory neuron that senses pain (i.e., signals pain when it depolarizes). It has an RMP of -65 mV.

• What would happen to the RMP if you give it a drug that will activate $K^+$ leak channels? RMP would become more negative

• How does this affect sensitivity to pain? Neuron would require a larger stimulus to reach the threshold for action potential generation, leading to a decreased sensitivity to pain.

Summary

• $Na^+$/$K^+$ pump

• Non-gated (leak) $K^+$ and $Na^+$ channels responsible for the RMP

• 0 mV (outside cell)

• -65 mV (inside cell)

• Practice calculations on page 176