Technology of Patch-Clamp Electrodes

The extracellular patch voltage clamp technique has facilitated studying the currents through single ionic channels from a wide variety of cells. In its early form (Neher and Sakmann, 1976 ), the resolution of this technique was limited by the relatively low [∼50 megohm (MΩ)] resistances, which isolated the interior of the pipette from the bath. The high resolution that can presently be achieved with the patch-clamp technique originated with the discovery (Neher, 1981 ) that very high resistance seals [tens or even hundreds of gigaohm (GΩ)] can form between the cell membrane and the tip of a clean pipette when gentle suction is applied to the pipette interior. Although the precise mechanisms involved in this membrane-to-glass seal are still not fully understood, the importance of the gigaohm seal is obvious. The high resistance of the seal ensures that almost all of the current from the membrane patch flows into the pipette and to the input of the current-sensitive head-stage preamplifier. It also allows the small patch of membrane to be voltage-clamped rapidly and accurately via the pipette, and the mechanical stability of the seal is vital to the whole-cell voltage clamp technique. Of equal importance, the high resistance of the seal greatly reduces the noise it contributes to single-channel measurements.