ABSTRACT

Advance in neuroscience is often techniques-driven. One of the best illustrations of this principle is provided by the story of the patch-clamp technique. Patch-clamping is the modem substitute for microelectrodes, although some things are done better with microelectrodes. Whole-cell recording of ionic current is the patch-clamp equivalent of experiments with ‘sharp’ intracellular electrodes. Better voltage-clamping means that fast currents are recorded more accurately and the cell’s membrane potential is more tightly controlled by the electronics of the amplifier. Better solution clamping means that the contents of the patch electrode diffuse more rapidly and completely into the cell. Traditionally, patch-clamping was restricted to cultured or acutely dissociated cells, because they lack much of the connective tissue and other impedimenta to the approach of a patch electrode. In one type of experiment, molecular biology reagents are mixed with the solution in the patch electrode, which is then used to obtain a whole-cell recording from the cell of interest.