Exploring the Seizing Neuron: Cell Neurophysiology

[zoobyshoe]

In my continuing research on seizures I came cross an article that goes into great technical depth. I'm wondering if anyone can read the following and expand and elucidate some of the biological terms.

"The cellular neurophysiological correlate of an interictal epileptiform discharge in single cortical neurons is the paroxysmal depolarization shift (PDS). The PDS is characterized by a prolonged calcium-dependent depolarization that results in multiple sodium mediated action potentials during the depolarization phase, and it is followed by a prominent after hypopolarization, which is a hyperpolarized membrane potential beyond the baseline resting potential. Calcium dependent potassium channels mostly mediate the afterhyperpolarization. When multiple neurons fire PDSs in a synchronous manner, the extracellular field recording would show an interictal spike.Calcium-dependent depolarization?

Calcium dependent potassium channels?

Sodium mediated action potentials?

 

[Moonbear]

Since I don't know what your background is, I'm going to ask some questions rather than answer your question, otherwise I'm either going to risk starting out too technical and not at all helping, or starting out too basic and seeming condescending.

Have you ever taken a general biology class either in high school or at a beginning college level?

Do you have access to a general biology textbook? (Campbell's is a really good one if you need to find one in a library).

Do you know, at least in a general sense, what an action potential is?

Unless you answered yes to all three questions, my suggestion is for you to first look up action potentials in the chapter on the nervous system in a biology textbook. Read it very carefully and use the illustrations to help you understand. The reason I'm not jumping right into an explanation is it's somewhat complex and I think it's much easier to understand if you have illustrations in front of you providing a schematic of the process. A textbook should have enough basic information to give you an initial understanding of the terms you've asked about. If you then need further clarification, or if you were looking for more technical detail, I'll at least know where to start.

If you don't have access to such a textbook, maybe someone here knows of a decent link to a site that illustrates the changes in ion channels in action potentials. Actually, if anyone knows of a decent link for that, I'd like to know about it anyway. I'm always looking for good illustrative material for teaching, and that's something students rarely understand until they can visualize the process.

 

[zoobyshoe]

Thanks, Moonbear. I will familiarize myself with action potentials first and post back with further questions.

-zoob

 

[Moonbear]

Great! I'll keep an eye out for follow-up questions from you.

 

[Monique]

I'll explain some basics :)

An action current briefly depolarizes the membrane from about -70mV to 50mV. Basically what happens during an action potential is the following: voltage-gated Na+ channels are prompted to open, allowing a small amount of Na+ to enter the cell down its electrochemical gradient, this influx of positive charge depolarizes the membrane further, thereby opening more Na+ channels, causing still further depolarization. The electrochemical driving force for the flow of Na+ approaches zero, this is when all Na+ channels are open.

Now regulatory mechanisms kick in that save the cell from a permanent electrical spasm: automatic inactivation of Na+ channels for a few milliseconds (which also forces unidirectional traveling of the signal) and opening of voltage-gated K+ channels, which overwhelm the transient influx of Na+ by an efflux of K+.

Then there are voltage-gated Ca2+ channels, which are at the nerve ending. The plasma membrane at the terminal is depolarized, and causes the Ca2+ channels to open, the Ca2+ flows into the nerve terminal (as the concentration there is 1000 times smaller). This increase in Ca2+ in the cytosol, triggers the localized release of acetylcholine into the synaptic cleft.

The released acetylcholine binds to muscle cell plasma membrane, resulting in Na+ efflux, causing membrane depolarization. This then triggers the release of Ca2+ from the sarcoplasmic reticulum into the cytosol and results of contraction of myofibrils in the muscle cell.

Those are the basics of neuron signal propagation.. your paragraph should be much easier to understand now :)

 

[Monique]

Found a good textbook picture: http://www.docrevello.com/voltage_gated_ion_channel.gif

 

[hypnagogue]

How is the Na+/K+ equilibrium maintained? From that graph it looks like Na+ always comes in and K+ always goes out. How/when do the reverse processes happen?

 

[zoobyshoe]

I am still at work on my understanding of the seizing neuron. I found an excellent book with many illustrations and I am still trying to familiarize yself with the resting potential and the action potential both of which are quite complicated. I am currently pondering the saltatory propagation long the axon, which is quite fascinating.

 

[Moonbear]

Originally posted by hypnagogue
How is the Na+/K+ equilibrium maintained? From that graph it looks like Na+ always comes in and K+ always goes out. How/when do the reverse processes happen?

There is an ATP-dependent (i.e., requires the cell to expend energy) pump that moves sodium and potassium in the opposite direction of the diffusion.

Zoobyshoe, as you're reading through all that material, keep in mind the system you're studying is very dynamic. In other words, ions are moving all the time. It is the relative ratio of ions on the inside of the cell compared to outside the cell that is determining the charge. You can achieve a "negative" membrane potential by having less positive ions inside the cell than outside. It doesn't necessarily require having more negative ions. That's a concept that many college students have had trouble with, and if you understand that, then the rest gets a lot easier.

When a neuron is resting, there is a lot of sodium on the outside and a lot of potassium on the inside. There is also a little sodium on the inside and a little potassium on the outside. There are also negatively charged anions inside the cell (lots of them) and lots of chloride outside the cell (also negatively charged). It is easier for potassium to flow out of the cell than for sodium to flow into the cell, so overall, you get more positive ions flowing out than in. That is what gives you a negative resting potential...inside the cell winds up more negative than the outside because the positively charged potassium has flowed out.

When an appropriate stimulus comes along, such as a neurotransmitter binding to its receptor, this can open a "gate" on a sodium channel (a structure in the membrane that sodium can move through). This allows sodium to move very quickly into the cell and make the inside more positive. If enough sodium moves into reach a threshold, then this is what provides the stimulation to open lots more sodium channels and change the inside of the cell to a more positive charge than the outside. This rapid change to a relative positive charge inside compared to outside the cell is what is called the action potential. The cell then "recovers" by closing the sodium channels and opening potassium channels to let potassium out and make the cell more negative on the inside again (by letting out the positive ions). Because potassium channels are somewhat slow to close, you will get a hyperpolarization, in other words, more potassium will go out than is necessary to return to just the resting potential, so you wind up with an even lower charge inside the cell than you started with. Once the potassium channels close, the cell returns to its resting potential.

The propagation of this down the axon means that this process doesn't happen in the whole cell all at one time, but a depolarization and repolarization in one place triggers the next segment to depolarize. This is why the hyperpolarization at the end of an action potential is important. This helps prevent the action potentials from moving backward instead of forward down the axon.

Calcium comes into play at a synapse, which is the way two neurons communicate with each other. Most commonly, these are chemical synapses. Think of the neuron terminal as containing lots of tiny balloons (synaptic vesicles) filled with chemicals (neurotransmitters). Calcium helps these balloons attach to the membrane and open up a place to dump out their contents into the very tiny space between two cells (synaptic cleft). These chemicals then can attach to a receptor on the next cell, and this event opens up sodium channels and starts the whole process over again in the next cell.

Yes, this is a lot to absorb all at once. Now I hope you see why I didn't jump straight into this explanation until you had some pictures to look at. Hopefully now that you have some pictures in front of you, and have been reading the text, this will help clarify some places that tend to be tricky to understand. I'm glad you're finding it so fascinating! It's really fun stuff!