Question

How does the axon of a neuron establish resting potential? Explain the roles of the three proteins. Where are ions?

Answer 1

neurons have a resting membrane potential (or simply, resting potential) of about −30 to -90MV

Cell membranes are typically permeable to only a subset of ions. These usually include potassium ions, chloride ions, bicarbonate ions, and others. To simplify the description of the ionic basis of the resting membrane potential, it is most useful to consider only one ionic species at first, and consider the others later. Since trans-plasma-membrane potentials are almost always determined primarily by potassium permeability, that is where to start.

The resting membrane potential is determined by the uneven distribution of ions (charged particles) between the inside and the outside of the cell, and by the different permeability of the membrane to different types of ions.

Types of ions found in neurons

In neurons and their surrounding fluid, the most abundant ions are:

• Positively charged (cations): Sodium (Na+) and potassium (K+)
• Negatively charged (anions): Chloride (Cl−) and organic anions

In most neurons, K+ and organic anions (such as those found in proteins and amino acids) are present at higher concentrations inside the cell than outside. In contrast, Na+ and Cl−are usually present at higher concentrations outside the cell. This means there are stable concentration gradients across the membrane for all of the most abundant ion types.

This diagram represents the relative concentrations of various ion types inside and outside of a neuron.

• K+ is more concentrated inside than outside the cell.
• Organic anions are more concentrated inside than outside the cell.
• Cl- is more concentrated outside than inside the cell.
• Na+ is more concentrated outside than inside the cell.

How ions cross the membrane

Because they are charged, ions can't pass directly through the hydrophobic ("water-fearing") lipid regions of the membrane. Instead, they have to use specialized channel proteins that provide a hydrophilic ("water-loving") tunnel across the membrane. Some channels, known as leak channels, are open in resting neurons. Others are closed in resting neurons and only open in response to a signal.

Ion channels. The channels extend from one side of the plasma membrane to the other and have a tunnel through the middle. The tunnel allows ions to cross. One of the channels shown allows Na+ ions to cross and is a sodium channel. The other channel allows K+ ions to cross and is a potassium channel. The channels simply give a path for the ions across the membrane, allowing them to move down any electrochemical gradients that may exist. The channels do not actively move ions from one side to the other of the membrane.

Some ion channels are highly selective for one type of ion, but others let various kinds of ions pass through. Ion channels that mainly allow K+ to pass are called potassium channels, and ion channels that mainly allow Na+ to pass are called sodium channels.

What about Cl- and organic anions

There are chloride channels that allow Cl−ions to cross the plasma membrane, though we won't focus much on them in this article. The chloride channels are conceptually similar to the sodium and potassium channels described in the section above.

The situation is different for organic anions present in the interior of the cell. Often, these anions are negatively charged amino acid side chains in proteins. The proteins are typically large and bulky and remain trapped inside the cell. Thus, organic anions generally cannot cross the membrane like Na+and K+.

In neurons, the resting membrane potential depends mainly on movement of K+ through potassium leak channels. Let's see how this works.

What happens if only K+ can cross the membrane?

The membrane potential of a resting neuron is primarily determined by the movement of K+ ions across the membrane. So, let's get a feeling for how the membrane potential works by seeing what would happen in a case where only K+can cross the membrane.

We'll start out with K+ at a higher concentration inside the cell than in the surrounding fluid, just as for a regular neuron. (Other ions are also present, including anions that counterbalance the positive charge on K+ but they will not be able to cross the membrane in our example.)

Starting state:

Zero voltage across the membrane, as measured by a voltmeter with one electrode inside and one electrode outside the cell. The inside of the cell and the outside of the cell are separated by a membrane with potassium channels, which are initially closed. There is a higher concentration of potassium ions on the inside of the cell than on the outside. Each potassium ion (on either side of the membrane) is balanced by an anion, so the system as a whole is electrically neutral.

Where are the Na+ and Cl- ions?

For clarity, the diagrams in this section show only K+ and the anions (negatively charged ions) that counterbalance the positive charge on K+ We don't say exactly what types of anions these are, so some of them may be Cl−ions.

Many other ions that are not shown in the diagram may be present in the system, including Cl− and Na+ However, since these ions cannot cross the membrane, they will not influence the membrane potential. This is why we can ignore them as we focus on the special case where the membrane is permeable only to K+.

If potassium channels in the membrane open, K+ will begin to move down its concentration gradient and out of the cell. Every time a K+ ion leaves the cell, the cell's interior loses a positive charge. Because of this, a slight excess of positive charge builds up on the outside of the cell membrane, and a slight excess of negative charge builds up on the inside. That is, the inside of the cell becomes negative relative to the outside, setting up a difference in electrical potential across the membrane.

System moving towards equilibrium:

If K+ can cross via channels, it will begin to move down its concentration gradient and out of the cell. (Channels are shown opening, potassium is shown moving from the interior to the exterior of the cell through channels.)

The movement of K+ ions down their concentration gradient creates a charge imbalance across the membrane. (The potassium ions that have crossed from the interior to the exterior of the cell are not partnered with anions on the outside of the cell. They line up along the membrane on the outside, and the unpartnered anions they left behind on the inside line up along the membrane on its inside face. The voltmeter now registers a slight negative voltage.)

The charge imbalance opposes the flow of K+ down the concentration gradient.

For ions (as for magnets), like charges repel each other and unlike charges attract. So, the establishment of the electrical potential difference across the membrane makes it harder for the remaining K+ ions to leave the cell. Positively charged K+ ions will be attracted to the free negative charges on the inside of the cell membrane and repelled by the positive charges on the outside, opposing their movement down the concentration gradient. The electrical and diffusional forces that influence movement of K+across the membrane jointly form its electrochemical gradient (the gradient of potential energy that determines in which direction K+will flow spontaneously).

Eventually, the electrical potential difference across the cell membrane builds up to a high enough level that the electrical force driving K+ back into the cell is equal to the chemical force driving K+out of the cell. When the potential difference across the cell membrane reaches this point, there is no net movement of K+ in either direction, and the system is considered to be in equilibrium. Every time one leaves the cell, another K+ will enter it.

Both K+ and Na contribute to resting potential in neurons

As it turns out, most resting neurons are permeable to Na+and Cl− as well as K+. Permeability to Na+, in particular, is the main reason why the resting membrane potential is different from the potassium equilibrium potential.

Let’s go back to our model of a cell permeable to just one type of ion and imagine that Na+ (rather than K+) is the only ion that can cross the membrane. Na+ t is usually present at a much higher concentration outside of a cell than inside, so it will move down its concentration gradient into the cell, making the interior of the cell positive relative to the outside.

Because of this, the sodium equilibrium potential—the electrical potential difference across the cell membrane that exactly balances the Na+concentration gradient—will be positive. So, in a system where Na+ is the only permeant ion, the membrane potential will be positive.

In a resting neuron, both Na+ and K+ are permeant, or able to cross the membrane.

• Na+ will try to drag the membrane potential toward its (positive) equilibrium potential.

• K+ will try to drag the membrane potential toward its (negative) equilibrium potential.

You can think of this as being like a tug-of-war. The real membrane potential will be in between the Na+equilibrium potential and the K+equilibrium potential. However, it will be closer to the equilibrium potential of the ion type with higher permeability (the one that can more readily cross the membrane)