INTRODUCTION TO THE MEMBRANE POTENTIAL

I.               Neuron Doctrine

a.     Neuron is the fundamental structural and functional unit of the central nervous system

(CNS)

b.     Neurons are discrete cells that are NOT continuous with one another; communicate via electrical and chemical transmission

c.     Parts of neurons—dendrites, soma, axon

i.        Dendrites— branched projections of a neuron; conduct the electrochemical stimulation received from other neural cells to the cell body

ii.      Soma—large, rounded portion of the neuron containing the nucleus (important for gene expression and protein synthesis)

iii.     Axon—long thin projection of a neuron that conducts electrical impulses (action potentials) away from the soma to the axon terminal

1.     Axon terminal is the distal end of the axon that forms the pre-synaptic component of the synapse (specialized composition for NT release)

2.     Axonal transport—limited if any protein synthesis occurs in axons, so essential proteins must be transported from the soma down the axon … facilitated by kinesin and dynein

3.     Axon’s are covered in a myelin sheath, provided by glia (oligodendrocytes or Schwann cells); myelin facilitates electrical conduction down the axon at nodes of Ranvier

iv. Membrane—hydrophobic barrier (lipid bylayer) that encloses the cytoplasm and cellular organelles; membranes contain variable proteins within the lipid bilayer that allow ions and small molecules to be transported into and out of the cell

1. Prototypical cytoplasm in neurons is composed of high K+ and low Na+ relative to the extracellular solution. Extracellular fluid contains high Na+ and low K+ 

v. Synapses—communication between neurons occurs at synapses, usually between an axon terminal and a dendrite; can be chemical (predominant in the CNS) or electrical

-Synapses are composed of the pre-synaptic axon terminal and post-synaptic dendritic spine

Membrane Potential  

II.             Membrane Potential

a.     Neurons exhibit a voltage difference across their plasma membrane known as a membrane potential (~ -65 mV in most neurons)

b.     Membrane potential results from the unequal distribution of electrical charge (carried by ions) on the two sides of the membrane

                                i. Electrical potential differences are measured in mV

c.     Neuronal membrane is an insulator and provides resistance to flow of ions between the intracellular and extracellular compartments

d.     Ion channels regulate membrane permeability to particular ions

i.      Ion channels are pores that span the neuronal membrane

ii.    Ions can only cross the membrane through ion channels or transporters (e.g., Na/K pump)

e.     The value of the membrane potential when a neuron is at rest is called the resting potential

i.        The resting potential is around -65mV

ii.      Negative membrane potentials indicate that the inside of the cell membrane is more negative than the outside

iii.     Hyperpolarized vs. Depolarized—When the membrane potential is more negative than the resting potential the cell is hyperpolarized; when it is less negative, when it is more positive the cell is depolarized

f.      Measure membrane potential (Vm) is produced by the flow of ions through leak channels -Channels that are always opened.

g.     The permeability of K+ leak channels is higher than the permeability of Na+. h. Equilibrium potential

i.      Assumes that the membrane contains ion channels selective for a single charged ion, X+, which is asymmetrically distributed across the membrane (there is a diffusion force for that ion to flow down it’s concentration gradient).  X+ will flow across the membrane from high to low concentration compartments until the build up of charge is sufficient to oppose net ion flow (electrical force)

ii.    Ex is called the equilibrium potential

At the equilibrium potential the diffusion and electrical forces cancel each other 

At the equilibrium potential there is no net current

All ions want to bring the membrane to their equilibrium potential Simplified equation: 

EX = 61.5mV log [X+]o

[X+]I

You do NOT need to memorize the equation, just remember that the concentration of the ion outside influences the eq. potential

Under normal conditions, the equilibrium potential for K+ is -80 mV and for Na+ +60 mV. This means that K+ will always try to flow "out" of the cell to  take its + charge out and make the inside more negative, whereas  Na+ will always try to flow "in" to make the inside more positive. If you increase the concentration of K+ outside the cell, the diffusion force pushing K+ outside will decrease, the equilibrium potential of K+ will be more positive than -80 mV, and more K+ will remain inside the cell producing depolarization If you increase the concentration of Na+ outside the cell, the diffusion force pushing Na+ inside will increase, the equilibrium potential of Na+ will be more positive than +60 mV, and more Na+ will flow inside the neuron making the inside more positive (depolarization)

Summary of resting membrane potential

Factors that influence the resting membrane potential of neurons

1.     Ion Concentration Gradients: The differences in the concentrations of ions (particularly sodium (Na⁺), and potassium (K⁺), inside and outside the neuron create potential differences. The Na⁺ concentration is higher outside the cell, while K⁺ is higher inside.

2.     Selective Permeability: The neuron's membrane is more permeable to K⁺ than to Na⁺ at rest. This selective permeability is mainly due to the presence of potassium leak channels that allow K⁺ to flow out more easily, contributing to a negative charge inside the cell.

3.     Sodium-Potassium Pump (Na⁺/K⁺ ATPase): This active transport mechanism pumps 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell, helping to maintain the concentration gradients essential for the resting membrane potential.

4.     Leak Channels: These channels allow certain ions to move across the membrane passively. K⁺ leak channels play a significant role in establishing the resting potential by allowing K⁺ to exit the cell.

Sodium potassium pump

The sodium-potassium pump (Na⁺/K⁺ ATPase) is a critical membrane protein in neurons and other cells that helps maintain the resting membrane potential and cellular homeostasis. 

•       The pump spans the cell membrane and is composed of multiple subunits

•       The subunits contain specific binding sites for sodium and potassium ions, as well as ATP.

•       The pump actively transports 3 sodium ions (Na⁺) out of the cell and 2 potassium ions (K⁺) into the cell for each cycle.

•       This movement is against their respective concentration gradients, which requires energy (ATP).

Ion selectivity

What produces selectivity to Na+ or K+?

The Na+ channel has a pore that allows 1 Na+ and 1 water of hydration to pass through. The size fits perfectly the Na and water molecule

The K+ channel strips the K+ from its water of hydration and only allows K+ to pass through. This prevents the Na+ with its water of hydration to pass through this channel