Learning objectives
- Why knowledge of signal transduction is important
- principles of the resting membrane potential
- principles of action potentials
- action potentials in aged neurons
- mode of action of lidocaine and cocaine
- gap junctions: shape and function
- the chemical synapse
...
Neurotransmission
Neurotransmission is the ongoing communication between neurons via neurotransmitters.
Disturbances in this communication is nearly always the cause of many neurological and psychiatric
diseases. Knowledge of signal transduction is key to the development of medication and
therapies/interventions.
Electrical signals between neurons is possibly only due to uneven distribution of charged ions inside
versus outside the neuron —> the resting membrane potential.
This separation is possible thanks to impermeable (bilayer) lipid membranes and well-controlled
exchange via specific transmembrane channels.
Channels can be opened by:
- Binding of neurotransmitters
- Phosphorylation (mostly on inside, cytosol side)
- Changes in voltage
- Mechanical stimuli
Basically there are two gradients:
- Concentration gradient
- Electrochemical gradient (gradient of electrochemical potential, usually for an ion that can
move across a membrane)
There are two crucial factors for ion exchange:
- Differences in ion concentrations
- Differences in electrical charges (indicated by the equilibrium potential (E ion))
Ion Ratio out : in
K+ 1 : 20
Na+ 10 : 1
Ca2+ 10.000 : 1
Cl- 11.5 : 1
During resting membrane conditions the distribution of ions inside and outside the cell is uneven,
which results in an electrical charge of - 65 mV between intra- and extracellular sides.
This is possible due to the closure of ion channels and selective transport over the cell membrane
(ATP-dependent). Maintenance of this difference in ion distribution is costly (energy and hence ATP-
wise).
These concentration gradients are also maintained by ion pumps which are energy dependent. No
energy —> no difference in membrane potential —> no brain activity. This happens in case of a
stroke.
, A very important ion pump is the sodium-potassium pump which also maintains the -65 mV —> K+
in, Na+ out.
Action potentials
Before and after the action potential,
the neuron is at its resting membrane
potential of -70mV. The action potential
itself can be divided into three phases:
- rising phase
o 3/4/5 (overshoot)
- falling phase
o 6/7
- after-hypolarization phase
(undershoot)
o 8/9
A question was why voltage-gated Na+
channels could close when the cell was
depolarised while depolarisation is the
stimulus for Na+ channel opening and
not closing. The answer is that these Na+ channels have two gates to regulate ion movement
rather than a single gate, these gates are called activation gate and the inactivation gate and they
flip-flop back and forth to open and close the Na+ channel.
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