An Overview of Voltage Clamp

Voltage clamp is an essential tool in any electrophysiology lab. It is used to look at the currents entering and exiting a cell at a set, or "clamped", voltage. First, I will explain the basic methods behind voltage clamp. Then, I will explain the uses of it.

How do I use voltage clamp?

The most important aspects of voltage clamp are shown in the diagram below, taken from here. The brown and beige sphere at the center of the stage is the cell from which we record. Finely tipped glass pipettes pierce the membrane of the cell which reseals against the surface of the glass. The metal electrodes are bathed in a solution inside the pipettes that become continuous with the cytoplasm inside the cell once the cell is punctured. The electrode on the right, the voltage electrode, records the voltage of the inside of the cell relative to the voltage outside of the cell at any given time. This signal is sent to the computer. Whenever the voltage inside of the cell deviates from a preset number (e.g. 80 mV), the computer then delivers a current back to the cell that returns the voltage back to that predefined value. The process is very quick.

By measuring the amount of current it takes to return the cell voltage back, we can measure the amount of current that is passing into or out of the cell at the set voltage. This is useful in a number of applications, some of which are explained in the next section.

What are the uses of voltage clamp?

Voltage clamp and its spin-offs have a wide range of applications in electrophysiology. As explained above, one application is the ability to record currents in and out of cells at given voltages. Resting membrane potentials can also be recorded, where the voltage is not clamped to any number. By using a similar method called patch clamp, in which a patch of the membrane is sealed onto the end of a glass pipette, scientists can even record the currents passing either direction through a single protein channel. And with even more advanced methods, such as dynamic clamp, we can simulate conductance changes in order to see how the cell would respond if the composition of its ion channels were different.

Through voltage clamp, we can elucidate a large variety of cellular mechanisms and behaviors. Some scientists use voltage clamp to look at how mutations in heart ion channels change the way a cell behaves under different voltages. Other scientists use voltage clamp to look at the behavior of neurons under simulated synaptic stimulation. How do you or would you like to use voltage clamp in your research?

Posted October 25th, 2010 in Neuroscience, Science.

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