Excitable cells and their biochemistry

David Taylordcmt@liv.ac.uk

http://www.liv.ac.uk/~dcmt

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

Learning objectives

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)

Resources

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 Cl-

• Intracellular 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

-70 mV

-55mV

+40mV Fully permeable to Na+(+40mV)

Fully permeable to K+ (-90mV)

1mS

Resting membrane potential(-70mV)

The depolarisation needs to be big enough to open the voltage activated sodium channels.

If it isn’t nothing happens….

All or nothing….

The action potential e.g. in neurones

-70 mV

-55mV

+40mV

VANC open

VANC close Fully

permeable to Na+(+40mV)

Fully permeable to K+ (-90mV)

1mS

stimulus

Resting membrane potential(-70mV)

The action potential

-70 mV

-55mV

+40mV

VANC open

VANC close Fully

permeable to Na+(+40mV)

Fully permeable to K+ (-90mV)

1mS

stimulus

Resting membrane potential(-70mV)

gNa+

gK+

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…..

Small waves of depolarisation (epsp)

Or hyperpolarisation (ipsp)

Post synaptic potentials

1mS

10mV

1mS

10mV

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

Summation and transmitters are exceptionally well covered in Chapter 5 sections III and IV of Preston and Wilson (2013)

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

Long-term potentiation

p.400-401 Naish & Court (2014)

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)

How does LTP happen?

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

Receptors, neurotransmitters and neuromodulators

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!