Download Simplified view of how a neuron sends a signal

Simplified view of how a neuron sends a signal
Figure 1A shows a stylized neuron with cell body, axon (variable in length), and dendrites. Dendrites are extremely
thin, delicate extensions of the plasma membrane. In the drawing, upon receiving a stimulus from a cell to its left
(e.g. one in the eye's retina), the neuron would send a signal (impulse) down its axon, from left to right, to a target
cell, which would respond. The type of response would depend on the type of target cell: another nerve cell ( relay
the signal on to another cell), a muscle cell (contract), a secretory cell of a gland (release a hormone). There are
two concepts here to stress: (1) what the impulse (signal) is and (2) how it is transmitted from the neuron to the
target cell. Figure 1 is about the first; Figure 2 is about the second.
The plasma membrane of the neuron is polarizable, which means that an electrochemical gradient can be created
across it. We studied concentration gradients earlier in connection with membranes. An electrochemical gradient is
one that has a charge component as well as a concentration component. If the concentration of solute "X" is greater
on one side of a selectively permeable membrane than the other side, there exists a concentration gradient across the
membrane. But if X happens to be charged, then there is also an electrical gradient across the membrane, more
charge on one side than the other. Just as energy is required to create a concentration gradient, so is it required to
create an electrical gradient.
This story is about two cations: Na+ and K+. Initially, before the membrane is polarized (Figure 1C), there are 3
relevant conditions: (i) [Na+ ] is lower outside the cell than inside, (ii) [K+] is lower inside the cell than outside, (iii)
the net charge inside and outside is the same, even though both solutions certainly contain a variety of charged ions
and molecules. The neuron's plasma membrane has a carrier protein called the Na-K pump (Figure 1B). It uses
cellular ATP to simultaneously pump Na+ out of the cell and K+ into the cell (Figure 1D). However, it moves 3 Na +
for every 2 K+. So, the result is to polarize the membrane, by creating a charge separation, more positive outside
than inside (Figure 1E). This separation of charges is called a resting potential. The membrane is now polarized.
The neuron is prepared to send a signal (impulse); it's capable of doing so but waiting.
In order initiate (send) its signal the neuron must receive a stimulus of sufficient magnitude; i.e. a threshold must be
met before the neuron "fires." If a cell to the left in Figure 1A provides a sufficient stimulus, then protein "gates"
(see Figure 1B) in the plasma membrane open, and the separated Na + and K+ ions flood back across the membrane
(Figure 1F), instantaneously eliminating the electrochemical gradient and depolarizing the membrane. In this event
the resting potential is converted into an action potential. Those proteins gates close then, leaving the neuron
momentarily in the same state it was in at the outset (compare Figure 1G with 1C), i.e. no electrochemical gradient
and no resting potential. {A good analogy for this threshold concept: Remove a kitchen match from its box and
rub it against the friction strip on the side of the box. If you press gently, the match won't ignite. Try again with a
little more pressure. The match won't ignite until you apply enough pressure to create enough friction to heat the
match head enough (the threshold). And when the match head does ignite, it does so explosively and completely:
an "all or nothing" response.} The neuron, too, does not respond to an inadequate stimulus; but when its threshold
is met, it's resting potential is converted into an action potential completely, all or nothing.
An instant after this depolarization (gate opening) event occurs at the left end of the cell, it causes adjacent protein
gates in the membrane to open, which in turn cause others nearby to open and so forth. The result is a moving wave
of depolarization along the neuron's surface from left to right in Figure 1A: gate opening, followed by Na + and K+
flooding through the gates, followed by gate closing again. Analogy: a pebble dropped into a still pool of water
creates a wave at that spot. And without any more pebbles dropped, that initial wave affects the water nearby such
that the wave moves away from that spot on its own, a ripple effect. The action potential moves along the neuron's
surface from one end of the cell to the other, arriving ultimately at the end facing the target cell.
Before we go on to the target cell, it's necessary for this neuron to repolarize its membrane if it is going to be able
to send another signal (action potential). Therefore, immediately after the protein gates have re-closed, as noted
above, the Na-K pump protein molecules re-establish the electrochemical gradient (i.e. the resting potential). All of
the events described so far, and those about to come, occur in about 5 to 10 milliseconds. That is, this whole
complex sequence of events is so fast that a single neuron might perform its signaling function 100 to 200 times per
second.
Now, on to the target cell....
Note in Figure 2A that there is a very narrow space between the target cell and the tips of the neuron's dendrites.
That is, the neuron's plasma membrane does not actually touch the target cell's plasma membrane. This tiny area
where the two membranes lie so close together is called the synapse. The gap between the cells is called the
synaptic gap (Figure 2B); it's only several nanometers wide and is filled with interstitial fluid. When the neuron's
action potential (the moving wave of depolarization) reaches the right end of the neuron, at the tips of the dendrites,
a second type of protein "gate" opens, allowing Ca2+ ions to flood into tip of the dendrite.
In the tip of the dendrite are many vesicles, each containing many molecules of neurotransmitter. The sudden
influx of Ca2+ causes these vesicles to fuse with the membrane at the dendrite's tip, releasing the neurotransmitter
molecules into the synaptic gap (Figure 2C). The neurotransmitter molecules then move by diffusion across this
narrow gap and bind to specific protein receptors in the target cell's membrane. Just as each type of hormone
molecule is shaped so as to bind to (recognize) only one type of receptor protein, neurotransmitters are similarly
specific for receptors. A given target cell will respond to a particular neurotransmitter only if the target cell has the
proper receptor in its plasma membrane.
The binding of the neurotransmitter to the target cell's receptor then sets in motion a cascade of events within the
target cell. If the target is a muscle cell, for example, the response would be contraction of the muscle cell. If the
target cell were a secretory cell of a gland, then the response would be for the gland cell to produce and secrete
(release) its hormone.
This neurotransmitter signal is terminated when the neurotransmitter comes loose from the receptor and then is
either (i) destroyed by an enzyme in the gap or (ii) is reabsorbed by the neuron's dendrite, to be reused.
There are many different neurotransmitters, produced by different types of neurons. Acetylcholine is the
neurotransmitter which causes a muscle cell to contract. Some molecules once regarded as hormones are now
known to be released by some neurons; so those molecules are both hormones and neurotransmitters: adrenalin and
serotonin, for example. Some neurotransmitters are stimulatory, such as adrenalin, whereas others are inhibitory in
their effects, such as GABA (gamma-aminobutyric acid). Neurotransmitters belong to various groups (families) of
organic molecules. Some of them may have other functions as well. The common amino acid, glutamic acid, is
used in the synthesis of proteins in cells and functions as a neurotransmitter in the brain. Known also as glutamate,
this molecule is found in the common flavor enhancer MSG (monosodium glutamate). Maybe there's a connection
between mixed up nerve signals (headache pain) and MSG in foods?
Many substances, including medications and ‘recreational drugs,’ produce their effects by enhancing or blocking
neurotransmitter actions in the body. This is true about hormones as well. Hence, there's a great deal of interest in
studying these molecules; many illnesses stem from too much or too little neurotransmitter or hormone produced.
Further, it has been found that molecules that are structurally similar to neurotransmitters or hormones can produce
dramatic effects, positive or negative, in the human body. Such molecules are called structural analogues.
Example: anabolic steroids that are used by some bodybuilders and other athletes are structural analogues of
testosterone. Example: GHB (gamma-hydroxybutyric acid), a structural analogue of GABA, has a powerful
inhibitory effect in the brain and has been used nefariously to incapacitate people ( a form of ‘knock-out drops’).
Nitric oxide, NO, a special case. Though neurotransmitters and hormones are organic molecules as a rule, NO is
not. Further, unlike the others, it is a gas. Among its effects in the human body, it dilates arteries. Some medical
treatments tale advantage of that. For example, chest pain due to angina pectoris may be relieved by a nitroglycerin
tablet slipped under the tongue. The absorbed nitroglycerine is converted to NO, which dilates coronary arteries,
increasing blood flow (with more oxygen) to the heart muscle.