Excitable cells and their
biochemistry
David Taylor
dcmt@liv.ac.uk
http://www.liv.ac.uk/~dcmt
Learning objectives
 When you have worked through this you should be able to
 Remember the function of the cell membrane and definition of
membrane potential
 Describe the function of the axon and the definition of action
potential
 Describe the physiology of chemical transmission at the
neuromuscular junction
 Describe the physiology of synapses, excitatory and inhibitory,
CNS neurotransmitters, the post-synaptic potential, including
long-term potentiation as a special type of neuronal response
 Receptors, Neurotransmitters, Neuromodulators – only the most
important
Resources
 These slides are available with all my other lectures on
my website http://www.liv.ac.uk/~dcmt
 In the text books:
Chapters 1,2, and 5 in Preston and Wilson (2013)
Chapter 2 and 8 in Naish and Court (2014)
First
 Remember what the membrane looks like
Fig 2.34 in Naish and Court (2014)
Resting Membrane Potential
•
•
•
•
•
Cells in the body are mostly impermeable to Na+
and mostly permeable to K+ and ClIntracellular proteins are negatively charged and can’t
leave the cell.
When the cell is “at rest” the membrane potential is a
compromise between the charge carried by the
diffusible ions, and the concentration gradient for each
ion
Normally this is about -90mV, or -70mV in excitable cells
The action potential
 e.g. in neurones
Fully permeable
to Na+(+40mV)
+40mV
Resting
membrane
potential(-70mV)
-55mV
-70 mV
Fully permeable
to K+ (-90mV)
1mS
All or nothing….
 The depolarisation needs to be big enough to open
the voltage activated sodium channels.
 If it isn’t nothing happens….
The action potential
 e.g. in neurones
+40mV
VANC
close
Fully permeable
to Na+(+40mV)
VANC
open
Resting
membrane
potential(-70mV)
stimulus
-55mV
-70 mV
Fully permeable
to K+ (-90mV)
1mS
The action potential
VANC
close
+40mV
Fully permeable
to Na+(+40mV)
VANC
open
gNa+
gK+
stimulus
Resting
membrane
potential(-70mV)
-55mV
-70 mV
Fully permeable
to K+ (-90mV)
1mS
The wave of depolarisation
+
-
+
-
+
+
-
+
+
-
+
-
+
-
+
+
-
+
-
+
-
+
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
+
-
The synapse
Figure 8.28 from Naish & Court (2014)
At the synapse
•
•
•
•
•
In response to depolarisation
Voltage-dependent Ca2+ channels open
Which allows vesicles containing
neurotransmitters to fuse with the membrane
The neurotransmitter crosses the synaptic cleft
And binds to receptors…..
Post synaptic potentials
 Small waves of depolarisation (epsp)
10mV
1mS
 Or hyperpolarisation (ipsp)
10mV
1mS
Summation
 Excitatory post synaptic potentials (epsp) are caused by
excitatory transmitters (e.g. glutamate NMDA receptor)
 Inhibitory post synaptic potentials (ipsp) are caused by
inhibitory transmitters (e.g. glycine receptor)
 And GABA (γ-amino butyric acid) opens chloride channels
(which makes the membrane less excitable)
 Summation can be spatial or temporal
 If there is enough depolarisation to open the voltage
activate sodium channels – then you get an action
potential
Summation and transmitters are exceptionally well covered in
Chapter 5 sections III and IV of Preston and Wilson (2013)
Long-term potentiation
 This is believed to be one of the mechanisms
underlying memory
 Repeated activity causes the production of more
receptors – thereby strengthening the connection
within the pathway/network
p.400-401 Naish & Court (2014)
How does LTP happen?
 Postsynaptically
 NMDA activation increases intracellular Ca2+
 Persistent activation of CaMKII (Calcium/calmodulin
dependent protein kinase) causes AMPA receptor
phosphorylation
 Phosphorylation of AMPA receptor makes the cell
(increasing conductance – i.e. increasing the effect of
glutamate)
 It also causes the insertion of more AMPA receptors
in the membrane (increasing the effect of glutamate)
Receptors, neurotransmitters and
neuromodulators
 Easiest to learn as you go along!
 But as you read about them or revise…, try and work
out whether they are
 Ionotropic – mediating ion fluxes
 Nicotinic ACh increasing Na+influx
 Metabotropic – acting through a second messenger
pathway
 Muscarinic Ach - which works through G-proteins to
modulate ion channel activity
Figure 5.3 in Preston and Wilson (2013)
Table 5.2 is excellent as an overview of possibilities
– but do NOT try to memorise it!