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Clamping down on the “clamp”

May 24, 2012

In my last post, I discussed the cutting edge experimental technique known as dynamic clamp. Neuronal modelers often encounter the term “clamp” when looking at electrophysiology articles, but it may be difficult to reconcile the term in its various uses. In this post I will try to clarify what “clamp” really means. First, there are only two general electrical procedures you can perform on a neuron: (1) measure the voltage or (2) inject a current. Each of these involves different forms of a clamp. Measuring the membrane voltage (procedure #1) requires a basic technique called “patch clamp” which is described on this webpage. If you read that webpage carefully, hopefully you will realize where the “patch” part of patch clamp comes from. It involves isolating a small area (patch) of a cell membrane.

Now where does the “clamp” come into play? Measuring the voltage is a passive procedure where we simply observe what the cell is doing. Injecting a current (procedure #2 from above) is used to experiment with a cell. There are three different approaches to current injection, and each one is referred to as a different type of clamp.

1. Current clamp: This is simply direct current injection. It is the process of choosing a constant current and injecting it using an amplifier. Using the term “clamp” here can be confusing, but it is a common way to distinguish it from #2 below. It is sometimes explained that the amount of current is what is being clamped (fixed). Note that the experimenter can simultaneously measure the membrane voltage using the same electrode that is used for the current injection. So technically, just observing the cell without injecting current is a form of current clamp where the injected current is zero.

2. Voltage clamp: This is a more sophisticated form of current injection. In the 1940’s, voltage clamp was a new technique that changed everything. A particular ion conductance might be voltage-dependent, so you want to be able to measure that conductance at different voltages to see how they’re related. To measure the conductance at a particular voltage, it’s much like measuring the resistance of a resistor. One way is to inject a current, measure the resulting voltage, and compute the resistance. (Or do the reverse.) The problem with a neuron is that the voltage won’t sit still! Once the voltage changes, it may change one or more of the conductances which will add more current and change the voltage. In order to keep the voltage constant, you can use a differential amplifier to monitor the difference between the desired voltage and the actual voltage. Then you simply inject more or less current to counteract any changes in voltage. This is the reason for the term “voltage clamp”. A good diagram can be found here on the website by Dr. Michael Mann (it’s Fig 3-19).

3. Dynamic clamp: This is still basically current injection like #1 and #2. It’s very much like voltage clamp in that the injected current is continuously adjusted to achieve some result. The difference is that you can do things that are much more complicated than just clamping the voltage at a constant value. My last post explains more about this.

So what is a “patch clamp” again? It is a general term that encompasses all three of the techniques listed above. Hopefully you now have a firm mental clamp on the “clamp”.

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