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Section 2: Why Are Cells Batteries?
In this second section of this chapter, we explore the origin of the cell membrane potential.
We've established that Cells are Batteries.
Batteries have an electrical potential. That's what makes them batteries. You can measure that electical potential, or voltage, in volts. With a AA battery, you'd get out your trusty voltmeter, and put one probe on the positive lead of the battery, and another probe on the negative lead, and measure the voltage. Easy.
With a cell, there's no positive or negative lead. You'd need to put one probe of your voltmeter INSIDE the cell membrane (that is, in the cytoplasm), and another OUTSIDE the cell membrane (that is, in the extracellular fluid or ECF). Then you'd measure the voltage gradient across that membrane. This voltage difference is called the membrane potential.
Now by convention, the extracellular fluid outside the cell is our reference point. It's defined as ground, or 0 V. So when we say a neuron's resting potential is -65 mV, we mean that it is 65 mV more negative inside the cell than outside.
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To get this answer, let's look closely at the cell membrane. It's a phospholipid bilayer. There are a bunch of proteins and glycolipids stuck into it. Some of them go all the way through, forming pores or channels. Some of these channels let some ions flow through - but they tend to be choosy about which ions they let through. Different channels let different ions through, and at different rates.
There are different concentrations of ions inside the cell compared to outside. That is, there are ion concentration gradients.
Inside the cell, in the cytoplasm, which is below the membrane in this diagram, we see there's a lot of potassium ions, and not a lot of sodium ions. So the potassium concentration gradient drives potassium ions to leave the cell when they are able.
In contrast, outside the cell, there are a lot of sodium ions, and not a lot of potassium ions. That's the sodium concentration gradient. It makes sodium ions tend to flow into the cytoplasm when able. But the membrane keeps these two spaces apart.
What causes these concentration gradients? One cause is that some of these protein channels allow only certain ions to passively diffuse through, but are NOT permeable to other ions. We call this selective permeability, and it is a passive process, meaning the cell doesn't need to consume energy to make it happen.
Then there are other channels that through active transport, consume energy (such as ATP) in order to build these gradients. The energy consumed allows these protein channels to drive some ions into the cell, and others out.
Some of the more important ion channels can exist in different states, meaning that the protein assumes one physical shape or conformation under one set of conditions, and another conformation under other conditions. Depending on the configuration or state of the channel, specific ions can either pass through, or be blocked from passing through. That is, the permeability of that channel to that ion changes. These channels have a variable permeability to a specific ion. Now when ions flow from one point to another, that creates an electrical current. So another way of phrasing this is that the ion channels change their resistance to the flow of ions, depending on their conformational state.
A simpler way of putting it, is the channels can be either open, or closed. If a channel is open, a particular ion is able to flow through it. If the channel closes, the ion can no longer flow through.
We know all of this because of a technique called patch clamping. It's a brilliant technique that uses very tiny electrodes to measure the flow of ions through microscopic protein channels in the cell membrane. It is not necessary to know anything more about it for this neuroanatomy course, and it has really doesn't have much clinical application. But, it is really cool. So if you are interested in learning more, I encourage you to read more about it. If you've got Nolte's The Human Brain, there's a nice summary of it on pages 152 and 153. A more detailed explanation can be found in Principles of Neural Science by Kandel et al. (ISBN: 0071390111).
Getting back to channels. Some channels can open, and close. They don't do this randomly. There needs to be a trigger to cause them to open and close. The trigger can be a change in the membrane potential, or a chemical, or mechanical deformation, or a heat change, and so forth. We call this gating.
For example, an important class of channels open and close depending on what the membrane potential is. If a change in membrane potential triggers a channel to open or close, then we say that channel is Voltage-gated. Channels that open when a particular chemical binds to them are ligand-gated.
Different channels are permeable to different ions. These combinations of selectivity and gating give rise to huge variety of ion channels. For example, there are voltage-gated sodium channels, ligand-gated chloride channels, and so forth. All kine gated channels with different selectivities.
And what's more, there are many many different subtypes of channels, coded by different genes. For example, we know that there are at least 9 different types of voltage-gated sodium channels (refer to PMID 19845672 on pubmed). Each behaves a little differently. And the nervous system uses this variability to give different structures different electrical characteristics.
It turns out, that not only are these very specific channels necessary for specific functions in the human body, but also, defects in or damage to these channels give rise to very specific disease states. For example, when antibodies attack a ligand-gated ion channel in the muscle membrane, the result is a disease called Myasthenia Gravis. Another autoimmune disease involving a completely different voltage-gated calcium channel in the neuron membrane is called Lambert Eaton Myasthenic Syndrome (LEMS). If a person is born with a mutation in a gene coding for a specific channel, they may go through life with a set of symptoms characteristic of that channel not functioning properly - we call these channelopathies.
Many toxins work by binding to very specific channels - and not to others. And this selective binding to very specific channels is also crucial to the functioning of certain pharmaceuticals.
All chemical processes tend towards equilibrium. At rest, ions are flowing into the cell at the same rate that they're flowing out. The Nernst equation lets us calculate the equilibrium potential of a particular ion. That is, voltage generated by that particular ion as a result of its concentrations inside and outside the cell, while in equilibrium.
R is the universal gas constant: R = 8.314472 E15 Joules per mole Kelvin
T is absolute temperature, in Kelvin
Z is charge (e.g., -1 for Cl or +2 for Ca)
F is the Faraday constant, the number of coulombs per mole of electrons: F = 9.64853399 E24×104 C/mol
One volt = 1 joule per coulomb
We can use the Nernst equation to calculate the equilibrium potential for Sodium. If we plug in these known values, including the concentrations of sodium ions in the extracellular fluid and in the cytoplasm for the cell at rest, we get the Sodium equilibrium potential, which is about +60 mV.
We can calculate the equilibrium potential for potassium as well: about -94 mV. You could look at the equilibrium potential for any ion you want. But that just gives us the individual voltages generated by each ion species. What if we wanted to know the actual value of the resting potential of a human cell?
The Goldman-Hodgkin-Katz equation (or Goldman equation) lets us do that. This is basically, a weighted average. The weights are provided by the variable P, where P sub X is the ion permeability for ion X. Note that P can change with time.
Using this weighted average of the contribution of each ion to the membrane potential, you can estimate the membrane potential. And what we can learn from this equation is that, at REST, the ion that has the greatest contribution to determining the resting potential is potassium. At rest, the potassium current is much greater than the sodium current.
A typical neuron resting potential is about -65 mV. This is much closer to the equilibrium potential of postassium (about -94 mV) than it is to that of sodium (about +60 mV).
However, it turns out that the sodium current is much more important for generating the neuron action potential, which will be addressed in another section.
So far, we've discussed passive processes. But the cell's battery would eventually run down if potassium wasn't pumped into the cell and sodium pumped out. This process requires energy. And there are proteins that use active transport to maintain these concentration gradients. The most important one is the sodium-potassium ATPase.
Sodium-potassium ATPase is a protein that spans the cell membrane. It is an active transporter. It gets energy from by the conversion of ATP to ADP. It uses that energy to take 3 sodium ions, and push them out of the cell into the extracellular fluid, while simultaneously taking 2 potassium ions from the extracellular fluid and transporting them into the cell. This is going on all the time, to re-establish those concentration and voltage gradients.
Nerve cells (neurons) and muscle cells (muscle fibers) are specialized cells whose cell membrane potential can change. These changes contribute to the basic functioning of these cells. Nerve cell processes can carry electical signals similar to how wires do.
Terminology:
By the end of this section, make certain that you understand what each of these terms mean, and can apply them appropriately.
- Resting Membrane Potential
- Permeability
- Resistance
- Voltage Gating
- Ligand Gating
- Nersnt Equation
- Goldman Equation
- Ion Pump
- Na+/K+ ATPase
Section 1: Cells are Batteries
Section 2: Why Are Cells Batteries?
Section 4: The Neuron Action Potential
Section 5: Muscle Fiber Action Potential
Section 6: Synapses and the Neuromuscular Junction (NMJ)
If you have any questions regarding this section, please ask them in the Neuroanatomy User Forum, or in the comments section at the bottom of this page.
