Transcript Neuron Structure and Function

Chemical synapses: post-synaptic mechanisms
Postsynaptic Membranes and ion channels
Ligand gated ion channels – a review
a. Resting K+ channels: responsible for generating the resting potential
across the membrane
b. Voltage- gated channels: responsible for propagating action potentials
along the axonal membrane
Two types of ion channels in dendrites and cell bodies are responsible for
generating electric signals in postsynaptic cells.
(c) Has a site for binding a specific extracellular neurotransmitter
(d) Coupled to a neurotransmitter receptor via a G protein.
More things to know about Ion channels
All the ion channels in question have a common feature
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A pore that allows the ion(s) in question to flow across the lipid bilayer
The pore is specific to a certain ion or ions
• Leak K+ channel only allows K+ ions to flow across the membrane
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Example: Acetylcholine (ACH) receptor allows Na+ to flow and the
glycine receptor allows Cl- to flow through the channel
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Ligand gated ion channels are different than voltage-gated ion
channels in that they are chemically gated ie via neurotransmitters
Binding a small chemical triggers the opening of the ion
channel
i) Na+ channels - excitatory (generates an excitatory postsynaptic
potential)
ii) Cl- channels - inhibitory (generates an inhibitory postsynaptic
potential)
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Important: The specificity of a transmitter response is a function of the
receptor type NOT the transmitter itself. (i.e. Ach can be excitatory
when binding to one type of AchR (NMJ)) and inhibitory when binding
to another type of receptor
Acetylcholine – general info
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Motor neuron transmitter at the
neuromusccular junction (NMJ) in
vertebrates
Present in brain (10% of synapses)
Packaged in high numbers in vesicles
1,000 to 10,000 molecules per vesicle at
the NMJ
Like all small chemical transmitters Ach is
synthesized and packaged into vesicles in
the synapse
The NMJ pre-synaptic side is packed full of
vesicles in the axon terminal
Many vesicles are released per action
potential to ensure a large safety margin so
that the muscle fiber (i.e. the postsynaptic
cell) will depolarize to beyond threshold.
Acetylcholine – receptor
• Officially called the nicotinic ACH receptor
(nAChR) because nicotine binds to this
receptor and activates it
• ligand gated ion channel
• has a depolarizing effect because Na+ is the
dominant ion through these channels
Acetylcholine – receptor
• generates an excitatory postsynaptic potential which at the NMJ
(motor end plate) is often called an "end plate potential“
EPP - end plate potential
Aka Excitatory Junctional Potential (EJP)
End plate potentials (EPPs) evoked by stimulation of a motor neuron are
normally above threshold and therefore produce an action potential
in the postsynaptic muscle cell.
nACHR – a closer look
• Most of the mass of the protein protrudes from the outer (synaptic)
surface of the plasma membrane
• The M2 alpha helix (red) in each subunit is part of the lining of the ion
channel
• Aspartate and glutamate side chains at both ends of each M2 helix
form two rings of negative charges that help exclude anions from and
attract cations to the channel. The gate, which is opened by binding of
acetylcholine, lies within the pore.
Aspartate
The Neuromuscular junction
The Neuromuscular junction
The Neuromuscular junction
• Arrival of an action potential at the terminus of a presynaptic motor
neuron induces opening of voltage-gated Ca2+ channels
• subsequent release of acetylcholine, which triggers opening of the
ligand-gated nicotinic receptors in the muscle plasma membrane
• The resulting influx of Na+ produces a localized depolarization of the
membrane
• leading to opening of voltage-gated Na+ channels and generation of an
action potential
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Synapses in the brain or central nervous system (CNS)
• A single synapse on a target is seldom found in brain
• Large neurons in the brain typically receive many inputs (1000 to
80,000 per cell)
• The inputs are integrated in the receiving neuron such that a "decision"
is made to pass on the information onto other cells
- this "decision" is often whether or not to generate an action potential
• each synaptic input usually only gives only a small depolarization, so
many inputs must cooperate (summate) to reach threshold to fire an
action potential
EPSP
An excitatory impulse, an excitatory post-synaptic potential raises the
membrane potential above rest
1. An excitatory impulse at a synapse on the soma causes a
depolarization of the whole soma including the beginning of the axon.
This is because the diameter of the soma or cell body is so large that
the internal resistance is very low so current flow extremely well
through the cell body
The beginning of the axon is also known as the spike initialization zone
or axon hillock and is packed with Na+ channels, an epsp of +15 to +20
mV triggers an action potential in the zone
2. An epsp generated on a dendrite will diminish in strength by the time the
current has reached the soma such that an epsp in a dendrite has less
of a chance of triggering an action potential than an epsp generated at
the soma
Due to the absence of voltage-gated Na+ channels in the soma and
dendrite of most neurons it is very unlikely that an action potential will
be generated in these regions
IPSP
• An inhibitory impulse is called an ipsp (inhibitory post-synaptic
potential) and lowers the membrane potential below rest
(hyperpolarizes)
• Synaptic transmission triggers the opening ligand gated Cl- channels or
indirectly through other mechanisms the opening of K+ channels
• Cl- flows into the cell
• K+ flows out of the cell
• Both increase the negative charge within the cell, hyperpolarizes the
soma
• Brings membrane potential further away from threshold and so it is
harder to trigger an action potential therefore inhibitory
• An ipsp on the dendrite will have less effect due to current loss than an
ipsp in the soma
CNS
Major ligand gated ion channels and their neurotransmitters
Glutamate - amino acid
• Most common excitatory neurotransmitters in central nervous system
• Neurotransmitter of NMJ in invertebrates (locust, giant axon of squid)
• Glutamate receptor - at least 3 different ligand gated ion channel
receptors for glutamate - all generate epsps as Na+ is the dominant ion
that flows after the channel is open
GABA - aminobutyric acid
• Major inhibitory neurotransmitter in the brain
• In some areas of cortex 1 in 5 neurons are GABAergic
• GABA receptors
- again many different types of receptors
- the more common GABA receptors are Cl - channels
- usually inhibitory causes an inhibitory postsynaptic potential (IPSP)
- reversal potential is the same as ECl - usually around - 70 mV
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Note: reversal potential is synonymous with equilibrium potential
cont…..
CNS
Glycine - simplest amino acid
• Major inhibitory neurotransmitter in the brainstem and spinal cord
• Glycine Receptor
- major receptor is a Cl - channel
- inhibitory
- like GABA receptor in that usually causes IPSPs
- blocked by strychnine (rat poison) which literally causes convulsions
and death as now the motor neurons are not inhibited and the
muscles contract without control. Yikes!
Cable properties again
• Dendrites extend 0.5 to 1 mm in all directions from soma and receive
signals from a large area
• 80-90% of all presynaptic terminals terminate on dendrites
• Most can't produce action potentials (too few or no Na+ channels)
• Transmit current by passive spread down dendrites to the soma
• Therefore the membrane potential decreases as move along dendrite
due to current loss thanks to our friends ri, rm and cm
• Dendrites have no voltage gated Na+ channels and cell bodies ie soma
have little or no voltage-gated Na+ channels current flow is solely
dependent on the Cable Properties of the dendrites and soma
Things to remember
• 1) loss of current across membrane (leaky membranes)
• dependent on the internal resistance (ri) and the membrane resistance
(rm)
• the length or space constant describes this property
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  rm / ri
• 2) loss of current (charge) due to capacitance properties of the
membrane
• cell membrane acts as a capacitor
• it takes time and current (charge) to charge the membrane capacitor
• the time constant describes this effect
τ = Rm x Cm
• details are in the lecture on cable properties 
Summation - CNS
• The postsynaptic effects of most synapses in the brain are not as large
as those at the neuromuscular junction
• In the CNS the postsynaptic potentials are usually far below the
threshold for generating postsynaptic action potentials
• Neurons in the central nervous system are typically innervated by
thousands of synapses, and the postsynaptic potentials produced by
each active synapse can summate together (in space and in time) to
bring the membrane to threshold for firing an action potential
Motor neurons and summation
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Each motor neuron synapses with multiple muscle fibers
The motor neuron and the fibers it contacts defines the motor unit
Summation
Summation of multiple epsps to bring the membrane potential to threshold
for an action potential.
Summation
A microelectrode records the postsynaptic potentials produced by the
activity of two excitatory synapses (E1 and E2) and an inhibitory synapse (I)
Electrical responses to synaptic activation
1. Stimulating either excitatory synapse (E1 or E2) produces a subthreshold
EPSP, whereas stimulating both synapses at the same time (E1 + E2)
produces a suprathreshold EPSP that evokes a postsynaptic action
potential
2. Activation of the inhibitory synapse alone (I) results in a hyperpolarizing
IPSP
3. Summing this IPSP with the EPSP produced by
one excitatory synapse (E1 + I) reduces the
amplitude of the EPSP, while summing it with the
suprathreshold EPSP produced by activating
synapses E1 and E2 keeps the postsynaptic
neuron below threshold, so that no action
potential is evoked.
Summation