Thursday, 30 August 2007

How do nerves (and muscles) establish a resting membrane potential?

In our quest to understand how neurones work, we've so far covered the functional anatomy of these cells. We've hinted at input and output areas, and whispered about transistors. Now it's time to be more forthright: neurones communicate by 'firing', and this 'firing' is in the form of a sudden change in the electrical potentials across their membranes.

If this makes no sense, worry not; we'll take it slowly. In this post, we'll just discuss the amazing phenomenon of how a cell comes to have an electrical potential difference across its membrane in the first place - the resting membrane potential.

Firstly, what is meant by "electrical potential across the membrane"? This is actually not difficult at all. All it refers to is that the inside of the cell has a different charge relative to the outside of the cell. In the case of many neurones, the inside of the cell might by 90mV less than the outside of the cell. Therefore there is an electrical difference between the two. Normally any electrical difference causes a current to flow, from the more positive side to the more negative side (by convention). But in our cells the electrical difference is usually only a potential difference, since there is a barrier to the charge flowing: the cell membrane. Putting it back together again, 'electrical potential across the membrane" actually can make sense now!

This might seem a strange fact to you. After all, electricity seems to be a distinctly 'unnatural' phenomenon, but here it is, the rock on which our brains and muscles are foundered. Neurones have a resting membrane potential (the electrical potential when the cell is not firing). When the cell does decide to fire, the electrical potentials change extremely rapidly, causing a chain of events that culminates in the neurone having some effect. Often this is simply signalling some information to other neurones, but it need not be. It may be to contract a muscle, for instance. In the next post, we'll discuss this 'firing'. For now, we'll just concentrate on how the resting membrane potential is created, for without a resting membrane potential, no firing would be possible.

The key to creating a resting membrane potential (RMP) is having a semi-permeable membrane. In other words, have a membrane that acts as a barrier to some substances, but not to others. Once you have this in place, interesting things start happening.

Take potassium (K+) for example, and say that the membrane is permeable to potassium, but not to other substances. Now, potassium is normally 25-40 times more abundant inside the cell than outside. Therefore, if the membrane is permeable to the ion, it will tend to diffuse outwards: But not forever. Since it is positively charged, and since no negatively charged ions can move out with it, there will very soon be a large positive charge on the outside of the neurone. After a short while, this positive charge is large enough to prevent further potassium from diffusing outwards (since 'like' charges repel each other). You could say that the chemical gradient is opposed by an electrical gradient. The end result? The outside of the cell has become more positive and the inside more negative (since the moved potassium is positively charged). In other words, there is an electrical potential on either side of the cell membrane. There is an equation, the Nernst equation, which can actually tell us how big the potential difference will be: -94mV. (The minus sign, by convention, means that the inside of the cell is more negative than the outside of the cell).

And this is basically how the cell establishes a RMP. Postassium is the main determinant of the RMP but the other ion to consider is sodium (Na+) . Its concentration is much higher outside the cell than in, so it tends to diffuse inwards. Like potassium, it is also positvely charged, but since its concentration gradient is in the opposite direction, it tends to make the inside of the cell more positive than before (counteracting potassium to some degree). However, it does not have nearly as strong an effect as potassium, only dragging the membrane potential from the -94 mV that potassium 'wants' to -86 mV.

The cell is permeable to potassium and sodium by means of potassium-sodium "leak" channels, through which the ions can, well, leak down their concentration gradiants. The leak channels are normally about a hundred times more permeable to potassium than to sodium, accounting for potassium's dominant status in determining the RMP. A small additional contribution to the RMP is made by the sodium-potassium pump, which is present on all cell membranes. It actively pumps 3 Na+ from the inside of the cell to the outside, and takes 2 K+ ions from the outside to the inside. Since it is taking more positively charged ions outside than it is bringing inside, it tends to make the RMP more negative (by an additional 4 mV; total: -90mV). Below is a diagram of the pump and the abovementioned 'leak' channel. (The 'ATP' refers to the body's currency of energy, and is to remind you that the pump obviously requires energy to work, since it is working against a concentration gradient.)To summarise nerves (and muscle cells) have a resting membrane potential. Rapid changes of this RMP occur for the nerve to fire (or the muscle to contract). And that'll be the topic of this section's next post.

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