Download “The Physiology of Excitable Cells”

How Real Neurons Work.
Computational Neuroscience
The Neuron : Overview
Thanks to Ramon y Cajal for the Neuron doctrine. (v. reticular theory).
Principles of Dynamic Polarization : Signals flow only in one direction.
Principle of Connectional Specificity : Neurons don’t make random connections.
These doctrines are now being called into question.
http://www.stewartartists.com/Pages/jjani_pc/jjnrns_pc.html
Overview (2)
Inside a Neuron.
1. Most differentiated
cells in the body.
2. Neurons develop
from epithelial cells.
3. Proteins are
synthesised in the
cell body.
4. They are modified in
the ER and Golgi
complex and
exported along the
axon.
Classification of Neurons.
Unipolar : Invertebrates.
Bipolar : Retina, Olfactory epith.,
Multipolar : e.g. motor neuron, pyramidal cell,
perkinje cell.
1.
The Cytoskeleton determines shape of neuron,
(disrupted in Alzheimer’s disease).
2.
Dynamic microtubules and microfilaments.
The Resting Cell Membrane
Ionic concentration gradient established by
Na/K ATPase Pump (100 ions/s).
K channels allow K to diffuse freely at a
certain rate.
K leaves the cell, so making the outside
positive and the inside negative.
This is self-limiting, as the positive external
charge opposes the further efflux of K+
I.E 2 forces : Channel Driving Force,
Electrical Driving Force, when balanced we
have the Equilibrium Potential of K+ .
http://www.du.edu/~kinnamon/3640/memb_pot_1.html
Ion Channels
Ion Channels are crucial for rapid membrane potential changes.
Ion Channels are proteins that span the cell membrane.
Q. How can a water-filled channel conduct at high rates and yet be selective to ions
surrounded by their waters of hydration? A.
PROPERTIES.
1.
Conduct Ions.
2.
Recognize and select
specific ions.
3.
Open and close in response
to specific electrical,
mechanical or chemical
signals.
4.
Rapid rate of flow 108 /s
5.
Opening and Closing of a
channel involves
conformational changes.
The Action Potential
http://www.blackwellscience.com/matthews/channel.html
An Action Potential is due to channels opening and closing in a
voltage dependent manner. Na channels open above a
threshold voltage.
The Sodium
Channel
The Ceylon Puffer Fish
Tetrodotoxin injected by Hodgkin and Huxley to block Voltage-gated Na Channels.
Cocaine
From coca leaves was the first anaesthetic, and also blocks Na+ channels with
lower affinity and specificity than tetradotoxin.
The K Channel
An outward K+ current increases the
repolarization rate of the action potential
Using Brownian dynamics simulations,
we follow the trajectories of interacting
ions in the potassium channel. With a
fast supercomputer, we simulate the
motion of 26 potassium ions and 26
chloride ions interacting through the
intermolecular potential. Here we apply
a potential difference across the channel
such that inside is positive with respect
to outside. The motion of each ion
during each discrete time step is
determined by, first, the net electrical
force acting on it; secondly, the frictional
force and, finally, random force
originating from incessant collisions of
the ion with its surrounding water
molecules.
1.
Variations in the properties of voltage-gated ion channels increase the
signaling capabilities of neurons.
2.
Gating of voltage gated ion channels can be influenced by cytoplasmic
factors, e.g. with Ca2+ channels.
An energy profile can be calculated based on molecular structure.
The Axon Hillock
Propagation
of Action
Potential
Is forwards, because of
the inactivated Na
channels.
AP travels at 80m/s
PASSIVE ELECTRICAL
PROPERTIES OF
NEURONS :
1.
Membrane Resistance determines the
magnitude of passive changes in membrane
potential. Related to [ion channel].
2.
Membrane Capacitance prolongs the time
course of electrical signals. Related to
surface area of cell.
3.
Membrane and Axoplasmic resistance affect
the efficiency of signal conduction.
Salutatory
Conduction
Chemical Synaptic Transmission
•When AP reaches a neurons terminal
It stimulates neurotransmitter release.
•Output signal is graded, amount of NT
released is determined by the number
and frequency of the action potentials.
•After release, NT diffuses across the
cleft to receptors on the post-synaptic
neuron. Binding then results in the postsynaptic cell generating a synaptic
potential.
The sign of this synaptic potential
depends on the type of receptors.
Pre-Synaptic Mechanisms
•Action Potential reaches Synapse.
•Synaptic terminal is depolarized.
•Voltage sensitive calcium channels open.
•Calcium enters synaptic terminal.
•Release of chemical neurotransmitter
Neurotransmitters Are Kept in
Vesicles.
Mechanism of Vesicle Docking.
Neurotransmitters.
Amanita muscaria
A Muscurinic Agonist.
Stimulates one of the
receptors that AcetylCholine
binds to.
The Black widow spider (Latrodectus)
is so toxic because of massive release
of acetylcholine from neurones.
Nicotine is a Nicotinic receptor
agonist.
Atropia Belladonna
is used to achieve
mydriasis, it has
atropine which is an
antagonist of
muscarinic
Sweating, salivation, abdominal cramps, bradycardia
receptors
Post-Synaptic Mechanisms
Neurotransmitter binds to receptors.
Change in ionic permeability of postsynaptic cell.
Change in membrane potential of
post-synaptic cell.
The same neurotransmitter can have
different effects depending on the
post-synaptic receptors present, i.e.
inhibitory or excitatory.
Many Types of NT Receptor Exist.
1. Ionotropic
2. Metabotropic
Dendritic Spines.
The video clip shows miniature
synaptic calcium transients visualized
with the fluorescent calcium probe
(fluo-3) in a spiny cultured rat cortical
neuron dendrite. The image shows
activity over a 10 sec period.
THE END