Samenvatting
Summary All cases of BBS1004
- Instelling
- Maastricht University (UM)
The cases are made according to the resources provided by the course.
[Meer zien]Voorbeeld 4 van de 148 pagina's
Voorbeeld 4 van de 148 pagina's
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Voorbeeld van de inhoud
Case 1 – Neurotransmission1. What is an action potential?
The inside of the neuronal membrane at rest is negatively charged in relation to the
outside. The action potential is a rapid reversal of this situation. The action potentials
generated by a patch of membrane are all similar in size and duration, and they do not
diminish (decrease) as they are conducted down the axon.
When the neuronal membrane is at rest, the Vm is about -65 mV. During the action
potential, the membrane potential briefly becomes positive.
- The rising phase is characterized by a rapid depolarization of the membrane.
This change continues until Vm reaches a peak value of about 40 mV.
- The overshoot is the part of the action potential where the inside of the neuron
is positively charges with respect to the outside.
- The falling phase of the action potential is a rapid repolarization until the
inside of the membrane is more negative than the resting potential. This is called
the undershoot.
- The last phase is the gradual restoration of the resting potential, the whole cycle
lasts about 2 msec.
The perception of sharp pain is caused by the generation of action potentials in certain
nerve fibers in the skin. The membrane of these fibers have a type of gated sodium
channel that opens when the nerve ending is stretched.
1) The thumbtack enters the skin
2) The membrane of the nerve fibers in the skin is stretched
3) Na+-permeable channels open
Because of the large concentration gradient and the negative charge of the inside of the
membrane, Na+ crosses the membrane through these channels. The entry of Na+
depolarizes the membrane. If this depolarization achieves a critical level, the membrane
will generate an action potential. The critical level of depolarization that must be
reached in order to trigger an action potential is called threshold. The depolarization
that causes action potentials arises in different ways in different neurons.
,There are a few types of causes for depolarization:
1) Entry of Na+ through specialized ion channels that are sensitive to membrane
stretching.
2) Entry of Na+ that are sensitive to neurotransmitters released by other neurons.
3) By injecting electrical current through a microelectrode, commonly used by
neuroscientists to study action potentials in different cells.
Generation of multiple action potentials
If we pass continuous depolarizing current into a neuron through a microelectrode, we
generate not one but many action potentials in succession. The rate of an action
potential generation depends on the magnitude of the continuous depolarizing current.
If we pass enough current through a microelectrode to depolarize just to threshold, but
not far beyond, we might find that the cell generates action potentials at a rate of 1 Hz. If
we increase the current, we find a higher rate. So, the firing frequency of action
potentials reflects the magnitude of the depolarizing current. The maximum firing
frequency is about 1000 Hz; once an action potential is initiated, it is impossible to
initiate another for about 1 msec. This period of time is called the absolute refractory
period.
It can be relatively difficult to
initiate another action
potential for several
milliseconds after the end of
the absolute refractory period.
During this relative
refractory period, the amount
of current required to
depolarize the neuron to action
potential threshold is elevated
above normal.
,Conduction of an action potential requires only a few
types of ion channels: a voltage-gated Na+ channel and
a voltage-gated K+ channel, plus some leak channels
that help set the resting membrane potential.
Action potentials begin when voltage-gated ion
channels open, altering membrane permeability (P) to
Na+ and K+.
1) Rising phase: sudden increase in the cell’s
permeability to Na+. An action potential begins when a
graded potential reaching the trigger zone depolarizes
the membrane to threshold (-55 mV) (3). As the cell depolarizes, voltage-gated Na+
channels open, making the membrane much more permeable to Na+. Because Na+ is
more concentrated outside the cell and because the negative membrane potential inside
the cell attracts Na+, it flows into the cell. This depolarizes the cell membrane, making it
more positive (4). In the top third of the rising phase, the inside of the cell has become
more positive than the outside, this is the overshoot. The action potential peaks at +30
mV, when Na+ channels in the axon close and potassium channels open (5).
2) Falling phase: Voltage-gated K+ channels open in response to depolarization. The K+
channels are much slower to open, and peak K+ permeability occurs later than peak Na+
permeability. By the time K+ channels finally open, the membrane potential of he cell has
reached +30 mV because of Na+ influx through the faster Na+ channels. At a positive
membrane potential, the concentration and electrical gradients for K+ favour movement
of K+ out of the cell. The membrane potential rapidly becomes more negative, creating
the falling phase (6). When the falling potential reaches -70 mV, the K+ permeability has
not returned to its resting state. Potassium continues to leave the cell through both
voltage-gated and K+ leak channels, and the membrane hyperpolarizes, approaching -90
mV. This is also called undershoot (7). Finally, the slow voltage-gated K+ channels close,
and some of the outward K+ leak stops (8). Retention of K+ and leak of Na+ into the axon
bring the membrane potential back to -70 mV (90). Sodium potassium pump brings it
back. 3 sodium goes out and 2 potassium goes in.
Action potential conduction
To transfer information from one point to another in the
nervous system, it is necessary that the action potential is
conducted down the axon. When a patch of axonal membrane
is depolarized to reach threshold, voltage-gated sodium
channels open and the action potential is initiated. The influx
of positive charge spreads inside the axon to depolarize the
near segment of membrane. In this way, the action potential
works its way down the axon until it reaches the axon
terminal, thereby initiating synaptic transmission. An action
potential propagates only in one direction, because the
membrane patch behind is in refractory period (orthodromic conduction). But an action
potential can be generated by depolarization at either end of the axon and can therefore
propagate in either direction (antidromic conduction).
, The voltage-gated sodium channel
The protein forms a pore in the membrane that is highly selective to Na+, and the pore is
opened and closed by changes in membrane voltage.
Structure:
- Created from a single long polypeptide.
- Has 4 distinct domains, each domain consists
of six transmembrane alpha helices. They
clump together to form a pore between them.
- The pore is closed at negative membrane
potential. When the membrane is depolarized
to threshold, the molecule twists into a
configuration that allows the passage of Na+
through the pore.
- It has a filter to be 12 times more permeable to
Na+ than to K+.
Function:
- Open with little delay
- Stay open for about 1 msec and then close
- They cannot be opened again by depolarization until the membrane potential
returns to a negative value near threshold.
2. What are Myelin sheaths?
Fat axons conduct action potentials faster, but
they take up a lot of space. A solution for this is
wrapping the axon with myelin. The myelin
sheath consists of many layers of membrane
provided by glial support cells → Schwann
cells in the peripheral nervous system (outside
the brain and spinal cord) and oligodendroglia
in the central nervous system. Myelin
facilitates current flow down the inside of the
axon, thereby increasing action potential
conduction velocity.
The myelin sheath does not extend continuously
along the entire length of the axon, it has breaks
where ions cross the membrane to generate action
potentials → Nodes of Ranvier. Voltage-gated
sodium channels are concentrated in the
membrane of the nodes. In myelinated axons,
action potentials skip from node to node, which is
called saltatory conduction, because they have
very few voltage-gated sodium channels. Only
membrane that contains these specialized protein
molecules is capable of generating action
potentials, and this is only found in axons.
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