Download Lecture 12 revised 3/2010 How do synapses influence whether or

Lecture 12
revised 3/2010
How do synapses influence whether or not the postsynaptic cell fires an action potential? Must explain
how they increase/decrease probability of action potential in postsynaptic cell for excitatory/inhibitory
synapses, respectively.
Reversal potential- the membrane voltage at which there is no net flux through the channels across the
membrane
The relationship between the reversal potential of the channel and the threshold for the action potential
of the cell determines whether receptors at a synapse are excitatory or inhibitory.
remember- the reversal potential depends upon the spectrum of the ions that the channel is permeable to
and the equilibrium potentials of those ions
e.g. a channel permeable only to Na would have a reversal potential equal to the Na equilibrium
potential
a channel permeable only to K would have a reversal potential equal to the Na equilibrium potential
a channel permeable both to Na and to K would have a reversal potential that is intermediate between
the equilibrium potentials of Na and K
nicotinic AChR is slightly more permeable to Na+ than K+, thus reversal potential isn’t exactly halfway between sodium and
potassium equilibrium potentials
Look at it this way- when the ligand causes the channel to open, ions that can move through the channel
will create a flux depending upon the difference between the membrane voltage and their equilibrium
potentials. This flux will push the membrane potential of the cell toward the equilibrium potential of
those ions- i.e. toward the reversal potential for the channel. Thus, the resulting flux might
hyperpolarize, depolarize or neither (latter if the membrane voltage is the same as the equilibrium
potential of the permeable ions).
The concept of reversal potential is useful for two reasons
1-by knowing the reversal potential of a channel and the threshold for the cell, you can predict whether
the receptor is excitatory or inhibitory
2- by determining the reversal potential for a receptor, you can deduce the ions it is likely to be
permeable to, and then confirm this by experimentally manipulating the concentrations of these ions and
determining whether this alters the reversal potential.
neurotransmitters cause conductance changes, resulting in PSC= postsynaptic current
which results in PSP= postsynaptic potential
in general, action of transmitter drives membrane toward Erev for the corresponding transmitter-gated channels
Thus, postsynaptic potentials alter the probability that an action potential occurs in the postsynaptic cell.
At nmj, PSPs only increase the probability.
But the NMJ is kind of a dumb synapse; it_s set up to be really reliable, to generate an action potential in the muscle cell
every time; lots of vesicles fuse resulting in a big PSP that pushes the cell past threshold.
In contrast, At CNS synapses- often just a single vesicle fuses, not even every time an AP comes down axon.
If neurons were set up the way the nmj is, they would only be relay stations... want them to be able to perform computations
by integrating information
at neuron-neuron synapses, can increase or decrease probability of an action potential depending upon the transmitters and
receptors present, thus 2 types of PSPs Fig 5.20, 5.21
EPSP- excitatory postsynaptic potential- incr probability of an A.P.
IPSP- inhibitory postsynaptic potential- decr probability of an A.P.
The factor determining whether a transmitter causes one or the other: type of channel(s) in postsynaptic membrane. But what
property of the channel(s)?
the ion(s) it is permeable to
i.e. the reversal potential of the receptor, which depends on the ions it is permeable to
and where the reversal potential is relative to threshold for that neuron, see fig. 5.19 20
Thus, while EPSPs always depolarize, IPSPs can hyperpolarize, depolarize, or produce no net current at all (just clamp the
cell at rest).
Most CNS synapses don’t behave like the NMJ- the PSPs due to a single synapse may only be a fraction of a millivolt.
Most neurons are innervated by thousands of synapses- thus the PSPs can sum together in space and time to determine the
behavior of the postsynaptic neuron.
Time summation over 5-15 msec, spatial summation over the soma is read out at the axon hillock- where action potentials are
initiated. This is where threshold will be read out, and the analog summation of the inhibitory/excitatory inputs is (or isn't)
converted into a digital signal (action potential). See fig. 5.20
So what do neurotransmitter receptors look like?
2 classes of Postsynaptic Receptors Fig 5.23
ionotropic receptors=ligand-gated ion channels
effects that last milliseconds
metabotropic receptors=G-protein coupled receptors
effects that can last minutes, hours, days
nicotinic Acetylcholine receptor Fig 6.3
nicotine=plant alkyloid; interferes w/ this receptor
other toxins- e.g. a-bungarotoxin (from banded krait- a poisonous snake)- irreversibly binds and
blocks- causes paralysis, snake gets to chow down
Torpedo- a marine ray-electric organ related to muscle; many cholinergic nerve terminals
innervating a postsynaptic membrane; like a stack of batteries- can generate a large voltage
ACh (acetylcholine) where found? parasymp (pre and post-ganglionic), symp (preganglionics), motor neurons, basal
forebrain cholinergics, brainstem nuclei
Basal forebrain cholinergics modulate fxn of forebrain, thalamus, etc. Alzheimer's loss of basalforebrain
cholinergics; drugs treat this
Note- in Alzheimer's patients, many other types of neurons also degenerate; treatments to activate cholinergic
system have been only marginally successful
ACh is synthesized by Choline Acetyltransferase (cytosol of axon terminal) from acetyl CoA and choline
AChEase (cholinesterase) is secreted into synaptic cleft by cholinergic neurons and some non cholinergic neurons;
terminates action by degradation (contrasts w/ most small molecule transmitters- termination by reuptake) into
choline and acetate.
choline taken up and reused, fig. 6.2
organophosphates inhibit AChEase: mustard gas (WWI), sarin (Japanese terrorists), some insecticides; death due to
respiratory paralysis
buildup of Ach depolarizes postsynaptic muscle cell, rendering it refractory to subsequent ACh release and causing
neuromuscular paralysis, asphyxiation
nicotine- (tobacco) binds skeletal muscle ACh receptors, but also affects brain (very addictive), causes dopamine
release in brain
muscarine (poisonous mushroom)- heart receptors
curare-(arrow tip poison- frogs of rain forest) blocks nicotinic receptors
atropine-belladonna plants- antagonizes ACh at muscarinic receptors (opthalmologists eyedrops related to atropine)
model for structure, fig. 6.3
5 subunits, 2α:β:γ:δ in muscle
neurons are 3α:2β
this receptor is reduced in abundance as a result of autoimmune antibodies directed to the receptor in
patients suffering from myasthenia gravis (Box 6B); unknown why these patients make these antibodies
Neurotransmitters- How get rid of following release? Have to terminate signal somehow. Degradation
and/or reuptake. Degradation by acetylcholinesterase in the case of acetylcholine.