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Download Simplified view of how a neuron sends a signal
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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.