Neuron Function

Electrical properties of Neurons

Membrane potential is a fundamental property of essentially all cells

There is inherently an excess of positive charge on one side of PM and excess negative charge on the other

Cells are more negative inside and more positive outside

Resting membrane potential

The electrical potential that exists between inside and outside

Describe as the cell having a negative resting potential

Measured in millivolts (mV) Place an electrode into cell Place second electrode outside cell

Electric Excitability

Cells of the body that have this Nerve cells Muscle cells Islet cells of pancreas

Certain types of stimuli trigger Rapid sequence of changes in membrane

potential This rapid sequence is called action potential

Action Potential changes

Electrical changes Changes from negative values to positive

values Changes back from positive to negative

Time it takes Occurs in a little over millisecond Rapid change allows quick communication

between cells located at times great distances from one another

Source of Resting Potential

Cytosol and extracellular fluid Contain different complement of cations and

anions Are different in overall composition

Extracellular fluids Watery solution of salts NaCl and KCl

Cytosol [K+] over [Na+] Anions of macromolecules Proteins/RNA

Basic Physical Principles

Diffusion - all substances tend to diffuse from high concentration to area of lower concentration

Electroneutrality - ions in solution are always present in pairs + with - (this is necessary to balance the charges

Tendency of oppositely charge ions to flow back toward each other is called potential or voltage

Basis of Concentration Gradients

Sodium Potassium ATPase pump - is present in all eukaryotic cells

Ratio or Stoichiometry for the pump 3 Na+ ions pumped out 2 K+ ions pumped in One ATP hydrolyzed

Na+/K+ ATPase Pump

Two subunits Alpha () subunits do

the pumping Beta () subunits are

glycoproteins anchoring the complex

Next slide for mechanism of pumping

Na+/K+ ATPase action 1

Several conformations are possible for a-subunits

As the shape changes the protein complex opens alternatively to inside / outside of cell.

Affinities for Na+ and K+ vary alsoThis mechanism is an ex. of antiport

Na+/K+ATPase action 2

Na+/K+ ATPase sequence

Open towards cytosol, -subunits have high affinity for Na+ ions

Once 3 Na+ bind ATP phosphorylates -subunits causing conformational change opening to the environmental face

At same time -subunits loose affinity for Na+ and it diffuses out to the environment

Na+/K+ ATPase sequence2

K+ affinity is increased in Phosphorylated form

2 K+ bind and this causes an increased rate of hydrolysis of PO4

-2 from .

Release of causes conformational shift of -subunits re-opening them to cytosol and releasing 2 K+

Electrical Excitability

The resting membrane potential is characteristic of all eukaryotic cells

Electrical excitability is characteristic of only some cells This is due to the response of these cells to

membrane depolarization These cells are electrically excitable because of

the presence of particular types of ion channels

Ion channels 1

These are integral membrane proteins that are capable of forming ion conductive channels through the lipid bilayer of PM

Channels are generally classified by the kind of ion they conduct Sodium channels Potassium channels Chloride channels

Ion Channels 2

Influence rate, but not the direction of ion flow

Common structural motif-helices pass through PMHydrophilic residues toward interior of channelHydrophobic residues toward lipids of PMTypical channel has six -helical passes through

PM

Ion channels 3

Controlling the opening and closing is called gating

Channels differ in the stimulus that causes them to open and how long they stay open Voltage gated channels - respond to specific voltage

changes across the PM; imp in AP Ligand gated channels - open when particular

molecules bind to the channel; imp in chemical communication between neurons across the synapse

Structure and Function of voltage gated channels

Voltage gated potassium channels Multimeric proteins- formed by the interaction

of four separate protein subunits When joined in the membrane these form a

pore for K+ ions

Voltage gated sodium channels One large protein - with four separate domains Each domain similar to K+ gate subunits

Common Features of Voltage Gates

Both kinds of channels Domains are subunits are made up of six

transmembrane -helices One of the -helices has charged amino

acids important in acting as a voltage sensor Changes in voltage across the membrane

cause these amino acids to shift The changes lead to openingThe changes lead to closing

Gated channels

Are specific for a single ionExperience an all or none phenomenon

Open channels conduct ions at maximum rate Closed channels do not conduct ions

Channel inactivation Channel closes in a way that does not allow it

to open again right away even if stimulated

Action Potentials

Electrical changes that occur when an action potential is generated are shown in

The squid axon is the experimental model for early studies

Human axon has slightly different potentials

Graph of Action Potential

Resting Neuron

First the resting neuron has to be stimulated

Depolarization causes the membrane potential to shift in a more positive direction

Most stimuli that have excitatory potential cause leakage of Na+ ions from the extracellular space into the cell

Threshold potential

If the depolarization is small (less than 20 mV the resting membrane potential is re-established

If the depolarization is greater than about 20 mV the cell reaches the threshold potential

At threshold potential the neuron commits to an action potential

Action potential changes

A rapid swing in membrane potential in the positive direction is observed to about 40 mV (35 mV in human).

This is followed by another rather rapid swing in the negative direction to a hyperpolarized -75 mV (-80 mV in human)

Then the resting potential is re-established

The ion movements of AP

The stimulus is usually bound to the leakage of Na+ ions into the cell through ligand gated channels (best example neurotransmitters cause this to happen)

Once this graded response reaches the threshold potential an AP is engaged

The rapid phase of depolarization occurs when voltage gated Na+ channels open

The ion movements of AP 2 Repolarization

At the apex of the AP current changes Na+ voltage gates slam shut K + voltage gates swing open K + is powered out of the cell by two forces

It runs down its concentration gradientIt is repelled strongly by the excess of positive charge in

the cytoplasm (remember Na+ ions just came screaming into this space)

The K+ ions over do it a little and the membrane becomes hyperpolarized

The ion movements of AP 3

Finally the Resting potential is re-established by the action of the Na+/K+ ATPase pump

Keep in mind this pump is running all the time so once the AP has passed it is the natural order for the resting potential to reform

There is a refractory period after an AP has passed

Graph of Action Potential

Y axis is change mVX axis time msD is Threshold PE is Resting PA Na+ voltage gates

open (depolarization)B Na+ voltage gates

close

Graph of Action Potential 2

B K+ voltage gates open

C - repolarizationDip in curve

hyperpolarized

Action Potentials final

Non-myelinated axon AP moves along entire length of axon

Myelinated axon (see figure in lab) Saltatory latin for dancing Saltatory AP moves from one Node of

Ranvier to the next Speeds up transmission