Download Neuron Function

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 (a) subunits do
the pumping
Beta (b) subunits are
glycoproteins
anchoring the complex
Next slide for
mechanism of
pumping
Na+/K+ ATPase action 1
Several conformations are possible for asubunits
As the shape changes the protein
complex opens alternatively to inside /
outside of cell.
Affinities for Na+ and K+ vary also
This mechanism is an ex. of antiport
Na+/K+ATPase action 2
Na+/K+ ATPase sequence
Open towards cytosol, a -subunits have
high affinity for Na+ ions
Once 3 Na+ bind ATP phosphorylates a subunits causing conformational change
opening to the environmental face
At same time a -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 a.
Release of causes conformational shift of
a -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
a-helices pass through PM
Hydrophilic residues toward interior of channel
Hydrophobic residues toward lipids of PM
Typical channel has six a-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 a-helices
One of the a -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 opening
The changes lead to closing
Gated channels
Are specific for a single ion
Experience 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 reestablished
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 reestablished
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 gradient
It 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 reestablished 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 mV
X axis time ms
D is Threshold P
E is Resting P
A Na+ voltage gates
open (depolarization)
B Na+ voltage gates
close
Graph of Action Potential 2
B K+ voltage gates
open
C - repolarization
Dip 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