What we'll see is that nerves exhibit an important generalphysiological phenomenon which is called ALL OR NONE PRINCIPLEwhich means that when you see a nerve impulse in a nerve fiber,you either see the whole entire thing in it's complete form orthere's nothing.
Then we'll talk about the cellular basis for the nerve impulse.In other words, what's actually happening in the membrane of thecell and the membrane-bound proteins.
Let's look at the general anatomy of the nerve cell or neuron.Basically the nerve cell has little extensions on it and then ithas one major extension that goes down to the end and then wehave some branches. The major extension is called the axon. Thisaxon is a very small microscopic structure. The largest ones thatare known are around a millimeter in diameter but most of themare much smaller than that. However, they can be incredibly long.They might in fact be several meters long. There are nerve axonsin the skin of the foot of a Giraffe that start in the spinalcord for example.
In general, what happens is the nerve impulse comes into thiscell body and has a variety of different impulses that are cominginto different nerves and some of that information tells thisnerve cell to send an action potential out. Some of thatinformation coming in may be telling it to don't send a nerveimpulse out. Action potential is the technical name for a nerveimpulse. So conflicting kinds of information comes into the cellbody, the cell body electrically adds up the plus' with thenegatives and then if the plus' outweigh the negatives then itsends out it's own action potential traveling along the axon.Well we can electrically stimulate this axon direct. We use amicroscopic glass tube which is filled with a salt solution sothat it can conduct electricity, this then stimulates the axon.It allows us to move this microscopic electrode around andphysically stimulate through the membrane itself. So we canelectrically stimulate this axon with a micro-electrode. And thensomewhere else along the axon we can measure what happens to amembrane potential because what's going to happen is that themembrane potential under certain circumstances will change. Sowhat I'm going to do is I'm going to draw a graph of 2 electricalreferences. We're going to look at millivolts and this is goingto be a record of what's happening in our senses - what happensin the axon. So the first one constitutes the response of thecell. And in the second graph, we're going to be measuring thestimulus, that is the intensity of the stimulus in millivolts.We'll have an electrical device called the stimulator and it'llhave some dials on the front of it and we can vary the size andduration of the stimulus with the signal that we apply to ourstimulator.
We're going to stick our measuring electrode into the axon andwe're going to find that the membrane-potential is somewherearound minus 70 millivolts. All cells have membrane potentialsand that's true for liver cells, fibroblasts, and any kind ofcell that has the 4 facts. And the cells are like the others,it's going to have a -70 potential.
What we're going to do is we're going to measure the intensity ofour stimulus by turning the dial and giving it a little stimulusand at the same time what we'll see is no change in the membranepotential of the axon. So if at first you don't succeed, try, tryagain.
So we'll give it a little bit bigger stimulus so a larger voltagepotential is applied across this membrane and once again still noresponse on the part of the membrane of the axon.
So we'll be brutal and give it an even larger stimulus and all ofa sudden, now we have a response. This is time which is about 1millisecond and this change in membrane potential is what we callan action potential. This is the potential difference in theelectrical gradient across the membrane of the axon and it'schanging so we call it an action potential. It starts out ataround -70, it goes up to somewhere around about 30, comes backdown somewhere around -90 and 10 milliseconds later it turns backto it's resting potential in the nerve.
We might be interested to know what happens if you apply an evenbigger stimulus. And what we're going to find is that there is nodifference in the appearance of magnitude of the time course ofthe action potential. The action potential gives us this"All or None" phenomenon. That's not the only kind ofresponse that our systems can give us. We're used to the otherkind of response which is called Graded Response. When you uselight, it can be dim or it can be bright. So some physiologicalphenomenon will show us graded response. Others give us the allor nothing response. Nerves gives us the all or nothing response.So we have some curve when we're dealing with the all or nothingresponse and we have some terms to describe the stimuli. And thesmallest stimulus that can/will produce a response is called athreshold stimulus. And of course there are terms that we use forone which is less than that which is the sub-threshold. And onesthat are larger than that are called supra-threshold.
Let's take a look at this action potential in a little moredetail. When you draw a graph, it's a good idea to be sure andlabel the axis. It's pretty easy for most biologists to rememberthe shape of the relationship but many claim they forget where onthe x-axis it is. Em means E for electrical volt and m formembrane. And this is measured in millivolts.
Next we start off with the membrane at it's resting level and themembrane is said to be polarized. That means 2 poles of opposingviews; there's an electrical difference across the membrane sounder resting conditions the membranes are polarized. And then wegive it a supra-threshold stimulus and what we see is a rapidincrease followed by a rapid decrease, followed by a period oftime when the membrane really is more polarized than at rest andthen gradually returns to the resting point.
The period of time when the membrane is more polarized thannormal is called the hyperpolarization.
In terms of the "gross function of a neuron" there are2 more terms. Each term is called the refractory period.Refractory period refers to the fact that the nerve cannotrespond.
1) Absolute refractory period - The nerve cannot be made torespond to any stimulus at all. The absolute refractory periodlasts for 1 millisecond. So it corresponds to the spike phase ofthe action potential. The nerve cell membrane, during the spikephase, cannot be caused to generate another action potential. Allof it's equipment is necessary to make that action potential intoa spike phase.
2) Relative refractory period - This is the period of time when asupra-threshold level stimulus can elicit an action potential. Athreshold level stimulus, the smallest stimulus that can producean action potential whose membrane is at rest, will not causeanother one during the relative refractory period. So you canproduce an action potential during this period. This period lastsfor 9 milliseconds. And it corresponds to the period ofhyperpolarization.
It makes sense. Let's say you are trying to stimulate this axonwhen the membrane is polarized at this level. You have to give ita larger stimulus in order to cause it to produce an actionpotential. So when the membrane is hyperpolarized, thesupra-threshold level stimulus will be required to produce anaction potential. In a relative refractory period, this happens.The significance of the relative refractory period is that it hasto do with how information about stimulus intensity istransmitted in the nerve system. If you can tell with your ownsenses whether a stimulus is a weak stimulus, a moderately strongstimulus or a very strong stimulus, take for example if we took asharp pin or something like that and it just barely touches yourskin, or it jams a little bit harder, you can tell thedifference. You can judge the intensity of sound. If the sound isvery loud, you can tell that it's really loud. If light is verybright you can tell that it's very bright. So obviously thenervous system has some way of telling the brain whether astimulus is a weak one or a strong one. And that's what I mean bytransmitting information about stimulus. What we do not find is aweak stimulus producing small action potentials and a strongstimulus producing a big action potential. That would be one wayto theoretically imagine how it works but it doesn't.
What the nervous system does is transmit information on theintensity of the stimulus and is codes it in terms offrequencies. Frequency modulated systems. So if the stimulus is aweak one, then the sensory cell that's receiving it will sendaction potentials at a fairly low frequency (for example: being abeep------------beep). A weak stimulus might be transmitted tothe brain at a moderate level stimulus (for example: being abeep-----beep-----beep). And a moderate level stimulus with eachbeep corresponding to that as beep---beep---beep and a veryintense stimulus being beep-beep-beep. So the intensity of thestimulus is proportional to the number of action potentials persecond.
If you have a very weak stimulus and it's just a threshold levelstimulus, then the interval/frequency of action potentials can'tbe less than 10 milliseconds. If you have a stronger stimulusthat is enough to cause the sensory to fire an action potentialduring it's period of hyperpolarization, then a stronger stimuluscan produce a smaller interval to the action potential.
Now what is the cellular basis for the action potential? Let'stalk about what happens in the membrane of this cell thatproduces this action potential.
Basically we know that at rest, the cell has a fairly highmembrane permeability to potassium. So let's graph the potassiumpermeability. That's the ease with which potassium can getthrough the membrane. We know that at rest the membrane has afairly high permeability to potassium and has a very lowpermeability to sodium ions. That's going to be true of any cellin the body. What distinguishes nerve and muscle cells from theother cells is that they have the ability to have a change intheir sodium permeability. In fact, the spike phase of the actionpotential is produced by an increase in sodium permeability ofthe cell. What happens to sodium permeability is that it goesvery high and then it drops right back down again by itself. Thehigh point of sodium permeability corresponds to the high pointin the action potential. And during the spike phase of the actionpotential, when the sodium permeability has reached it's maximum,the membrane of the cell is something like 600 times a millivoltsodium than it is to potassium.
Then the sodium permeability drops back down. Let's go back tothe diagram: High K concentration on the inside, negative proteinat rest, membrane is mainly on the inside, low K on the outside,high Na on the outside. And at rest we know that there are open Kchannels. Those are membrane-bound proteins, their function isfacilitated diffusion and they account for the K permeability toget through the lipid bilayer. Now what makes a nerve cell or amuscle cell different from most cells is that they also have Nachannels and these channels are normally closed. Simply stated,when the nerve cell is stimulated to the threshold, the Nachannel opens. Some how they physically change theirconfiguration so that now Na can come into the cell through thatchannel.
At first there are 2 driving forces bringing that Na in. 1)Negative charge on the inside. 2) Na concentration is much higheron the outside.
But as we can see from our graphs of the action potential, it'ssomething like a quarter of a millisecond or so. The membranegoes from being negatively charged to having no charge and thenit goes on to have a positive charge. So, at the peak of thespike, the membrane is positively charged. That is, so much Nahas come in that now the inside of the cell is positive relativeto the outside because there's a Na gradient. That is, the Naconcentration is higher on the outside during the spike phase,the Na channels are open, and Na coming into the cell moving downit's own concentration gradient causes the inside of the cell tobecome positive. Just like positive charges moving out of thecell makes the inside of the cell negative and the negativecharges going out of the cell makes the inside of the cellpositive when the sodium channels are open to allow that tohappen. And so it goes up to this +35 and that can be determinedby measuring the concentration of Na on the inside of the celland the concentration of Na on the outside of the cell.
Well, the Na channels open up and the further the membranepotential moves away from the resting value or the closer it getsto zero, the more Na channels open up. So you make the cell alittle bit positive or a little bit less polarized, move ittowards zero and some Na channels open up which makes it a littlebit more positive because a little bit of Na comes in and thatcauses more so what you have is this sort of cascading effect ofNa channels making the inside positive. That allows more Nachannels to open up and as more Na comes in, you get the spikephase and it goes up the spike very rapidly. At that point the Nachannels are spontaneously closed. They did their thing so theyautomatically close.
But there is something else that's going on all this time andthat is the increase in K permeability and this causeshyperpolarization. As soon as that membrane starts to move awayfrom the resting value, some new K channels open up. The cell hasK channels that are normally closed. That is, when the membranestops being as negative as it normally is, some of those Kchannels can open up. And they count for this transient increasein K permeability. For the length of the period of the relativerefractory period, this hyperpolarization is more negative thanit is at rest and it is explained by this increase inpermeability.
When the action potential goes positive, that is the membranepotential in this area goes positive, that triggers anotheraction potential in the segment of membrane next to it. So thisone generates its little action potential and that actionpotential then causes the next little segment of membrane. Thisis all one cell, one continuous membrane and the next littlesegment membrane makes its own action potential and so on. Thisprocess is called propagation - the spreading of the actionpotential along the membrane of the axon. That is the way inwhich information is transmitted from one place in the nervoussystem to another place in the nervous system. Action potentialspreads along the axons with each little segment of axon membranegenerating their own action potentials.
Most of the time you've got sensory information that's coming infrom the eyes, your ears, your nose, your sense of touch, yoursenses that tell you about the position of your body and soforth. That information is being transmitted to the spinal cordand along the spinal cord to the brain and that information getsprocessed in the brain. Then brain makes some kind of responseand it's going to send action potentials out along the axon downthe spinal cord and in many cases, that response is going to beproduced by a refraction of a muscle. When I ask you a question,you hear the sound waves, they hit your ear, your brain processesit, you understand the question, you know the answer to thatquestion so then it sends an action potential to your muscle andyou raise your hand.
Neuromuscular Junction:
The junction between a nerve and the muscle cells is theneuromuscular junction. It's very similar to the junction between2 nerve cells which is called a synapse (but one nerve cell cansend information to the other nerve cell in a synapse). Theneuromuscular junction is a similar structure, with similarfunction and it is found where a nerve cell innervates a musclecell.
This structure is tremendously larger in a neuromuscular junctionthan it is in synapse but functionally, the same kinds of thingshappen. You have the membrane of the muscle cell called thesarcolemma and it's indented in the area of the axon terminal.Located in the axon terminal are little tiny spheres of membranematerial called synaptic vesicles. The space between the axonterminal in the sarcolemma is called the synoptic cleft. Andthese little spheres (like tiny balloons) that are made out ofmembrane material, phospholipid bilayer, which is the rest of themembrane above the cell, are the synaptic vesicles.
The synaptic vesicles contain a particular chemical calledacetylcholine. In the case of a neuromuscular junction, thechemical found in the synaptic vesicles is ACH. It is a simplechemical that is found in the synaptic vesicles. This basicarrangement is going to be found in many places in the nervoussystem. The chemical found in the synaptic vesicles is not goingto be ACH. There are a number of other chemicals that are foundin the same place such as norepinephrine, and GABA. These arefound in the synaptic vesicles in synapse and they all go by thegeneral name of neurotransmitters. Neuro because they are foundin nerves and transmitters because they transmit or sendinformation; they carry information from the nerve cell to theother cell, in this case the muscle.
What happens when an action potential is propagated down theaxon, spreading along the axon? It gets to the axon terminal andsome specified number of these synaptic vesicles will be causedto fuse with the membrane of the nerve cell. They fuse and theyopen up and they dump the ACH out into synaptic cleft. This iscalled exocytosis. It does this in basically the opposite waywhich an amoeba ingests something. Just the membrane fuses, sothe wall of the synaptic vesicle (phospholipid bilayer) actuallybecomes part of the membrane of the cell and it just kind ofdumps this neurotransmitter (ACH) out into the synaptic cleft. Sowe have an electrical signal, the action potential that's comingdown the axon, and we have a chemical signal that's sending itinto the synaptic cleft. And it's going to be fused across thesynaptic cleft. Higher concentration over here on the side nearthe nerve cell, lower concentration on the side of the cleft nearthe muscle cell so there's a concentration gradient.
Now located in the membrane of the muscle cell is a receptormolecule. It has its own shape so that it can combine with ACH.When the ACH receptor has ACH in it, it causes anothermembrane-bound protein, which is located in the membrane rightnext to it, to open (this is the sodium channel which is normallyclosed). It does not allow sodium to come through unless there isan ACH combined with the ACH receptor. This is when some sodiumis floating around at high concentrations in the fluidsurrounding the cell. Some of the sodium can diffuse into theinside of the cell. Usually the inside of the muscle cell. NoticeACH does not come inside because it is much too big of a moleculeto get through the membrane. All it does is it combines with itsreceptor.
As long as there is ACH sitting here in the synaptic cleft, thenthe cell is going to be generating action potentials, and whathas to happen is something has to get rid of that ACH. So there'sanother membrane-bound protein that sits in here, it's an enzyme.The function of an enzyme is to catalyze a chemical reaction andthis enzyme is also called an acetylcholine esterase. Thiscatalyzes the break down of ACH into 2 separate molecules,acetate and choline. What's important about splitting the ACHdown into acetate and choline is that neither one of those 2parts can combine with the ACH receptor. So the ACH-esterase isessentially turning off the chemical signal that the ACHrepresents. It's breaking it down and the choline molecules thatare produced by that are going to fuse back across the synapsetaking it up into the nerve cell, putting it back into ACH andpackage it up in some more synaptic vesicles so that the nervecell can do this whole thing all over again.
So we have all 3 of the major types of membrane-bound proteins.We have a receptor molecule (ACH), a membrane-bound proteinthat's involved in transporting (in this case it's justfacilitated diffusion of Na). The ACH molecule does not form acovalent bond with the receptor. The random molecular movementcauses the ACH molecule to move around and a whole bunch of ACHmolecules get dumped out into the cleft as a result of a singleaction potential and some of those will bump into theACH-esterase and get split right away. Others will bump into thereceptor, cause Na channels to open, cause the action potentialin the muscle cell membrane to get started and then it'll breakloose from the receptor and kind of bounce around. Then they getinto the ACH-esterase.
So we start off with an electrical signal in the membrane of thenerve cell in the axon and then we have a chemical transmissionin the form of a neurotransmitter (ACH). You've gotmembrane-bound proteins that receive that.
I should add that this might be an example of an essay questionyou might see on the midterm. Where I would ask you to describethis. I will expect you to say "well the action potentialcomes down the axons, causes the synaptic vesicles to fuse withthe membranes of the ACH in the synaptic cleft, and provides ACHreceptor causing the Na channel to open up. The ACH-esterasebreaks it down, the Na channel slowly deposits depolarization ofthe muscle cell membrane and that action potential spreads underthe muscle cell membrane. There's some other things that go onafter that which is the other half of the question of how itworks. That's the level of detail that you should be prepared togive me on a test.