Transcript Lect11

Announcements
• Mid term room assignments posted to
webpage
Lecture 01
A – Ho
S361 (Pavilion)
Hoang – Lischka
S309
Lishingham - Ngui
S143
Nguyen – Seguin
S128
Sek – Zia
H305
Lecture 02
S319
A. Excitor
B. Inhibitor
Record voltage
Simple case:
Threshold
A
B
Vm
Depolarizing  excitatory
EPSP
Threshold
A+B=smaller
Vm
hyperpolarizing  inhibitory
IPSP
How to get hyperpolarizing
potential?
• Neurotransmitter receptor is permeable to
an ion whose Eion is more negative than
resting membrane potential
• usually Cl- or K+
Hyperpolarizing Synaptic Potential
+60 mV
0 mV
+
+
K+
-80 mV
More complex case:
Threshold
A
B
Vm
Why???
Depolarizing  excitatory
Threshold
A+B=smaller
Vm
Depolarizing  inhibitory
Reversal Potential
• Membrane potential at which there is no
net synaptic current
Measuring Reversal Potential
eg. Frog NMJ
Current source
+25
stimulus
Control resting
membrane potential
0
Reversal potential
-50
-100
Stimulate nerve
Record membrane potential
• Many neurotransmitter receptors are
permeable to more than one ion
– Non-selective
• The reversal potential depends on the
equilibrium potential and permeability of
each ion
– It will usually be between the equilibrium
potential of the permeable ions
eg. Acetylcholine channel
• Permeable to both K+ and Na+
• For Frog muscle:
• EK = -90 mV
• ENa = +60 mV
Neurotransmitter
receptor
ENa = +60 mV
K+
VmENa
+25
0
Reversal potential
Vm=Erev
-50
Erev>Vm>EK
-90
EK = -90 mV
VmEK
Na+
How can depolarizing potential be
inhibitory?
• Excitatory synapses have a reversal
potential more positive than threshold
• Inhibitory synapses have a reversal
potential more negative than threshold
How can depolarizing potential be
inhibitory?
Erev
Threshold
Erev
A
B
Vm
Example: Cl- permeable receptor
in a cell whose Vthresh >ECl- > Vm
Inhibition
• Channels of inhibitory synapses ‘shortcircuit’ excitatory synapses
• Because neurotransmitter channels will
drive the membrane potential toward their
reversal potential
• Neurotransmitters and receptors
• Synaptic Integration
Types of Receptors
1. Ligand-gated ion channels
•
•
•
Neurotransmitter binding to receptor opens an ion
channel
Directly changes the membrane potential of the
postsynaptic cell
Also known as ‘fast’ synaptic transmission
2. G-Protein Coupled Receptors
•
•
•
Transmitter binds to receptor which activates
intracellular molecules
Can directly or indirectly change the membrane
potential
Also known as ‘slow’ synaptic transmission
Neurotransmitter Receptors
Ligand-gated ion channels
Acetylcholine
Excitatory
(Nicotinic)
Glutamate
Excitatory
(AMPA, NMDA)
Serotonin
Excitatory
(5-HT3)
GABAA
Inhibitory
Glycine
Inhibitory
Neurotransmitter Receptors
G-Protein coupled receptors
(muscarinic)
Usually
excitatory
Glutamate
Variable effects
Acetylcholine
(metabotropic)
Serotonin
Variable effects
(5-HT1-7)
GABAB
inhibitory
Same neurotransmitter, different receptors
G-protein coupled receptor
receptor
direct effect

G-proteins


Open or close ion channel
indirect effect
GDP
GTP
Activate intracellular
molecules
Regulate other cellular functions
eg gene expression
What happens to neurotransmitter
after it is secreted?
• Acetylcholine
– Broken down by Acetylcholinesterase into
Choline and Acetate
– Choline transported back into nerve terminal
and resynthesized into Acetylcholine
• Glutamate
– Transported into glia or the nerve terminal and
converted to glutamine
• Serotonin
– A neurotransmitter used in the emotional
centres of the brain
– Prozac is a drug that inhibits the reuptake of
serotonin
– Therefore, Prozac makes serotonin remain in
synaptic cleft longer
Synaptic Integration
The sum of all excitatory and inhibitory
inputs to a cell.
1. Spatial Summation
2. Temporal Summation
Spatial Summation
• The addition of several inputs onto one
cell
A
B
A
B
A+B
A
B
A+B
Temporal Summation
Stim once
A
Stim twice
Stim twice
Synaptic Integration
Summation
Synaptic inputs
Soma and
dendrites
Axon Hillock
Passive current
flow
Above threshold?
Yes
Action Potential
Conducts down axon
No
Passive Current
Decays to zero
Summary
• Excitation and inhibition in relation to the
reversal potential
• Fate of neurotransmitters after release
• Types of transmitters and their receptors
• Synaptic integration leading to action
potentials