The AXOCLAMP-2A Microelectrode Clamp can be used as a dual channel microelectrode probe, or as a microelectrode voltage clamp. Voltage clar, ping is a powerful technique for the control of membrane potential and for the investigation of processes aifecting membrane conductance. Voltage clamping has traditionally been performed using two intracellular microelectrodes and the AXOCLAMP-2A can be used for this purpose. The AXOCLAMP-2A can also be used for discontinuous single-electrode voltage clamping (dSEVC) and for continuous single-electrode voltage clamping (cSEVC). A single-electrode voltage clamp (SEVC) is more convenient to use than a two-electrode voltage clamp (TEVC) in very small cells and cells which cannot be visualized. A particular advantage of a dSEVC is that the voltage drop due to current flow through the series component of cell membrane resistance (Rg) is not clamped. In addition, for both types of SEVC instabilities due to coupling capacitance and coupling resistance between two microelectrodes do not arise. The disadvantages of a dSEVC compared with a TEVC are that the response speed is slower, the maximum achievable gain is lower, and the noise in the current and voltage records is greater. The design of the AXOCLAMP-2A reduces these disadvantages towards their theoretical minimums, thereby allowing singleelectrode voltage clamping to be performed in the many situations where conventional voltage clamping is not suitable. . A. cSEVC is as low in noise as a TEVC but has a severe disadvantage in that the voltage drop across the microelectrode is clamped unless compensation is made. Since the required compensation is never perfect, the cSEVC can only he used when the electrode resistance is very small compared with the cell input resistance. These favorable conditions can often be achieved by the whole-cell patch technique. " Because of the AXOCLAMP-2A's advanced design, it itself does not limit the achievable performance. Instead, the dominant factor affecting SEVC performance is the microelectrode. Users of the AXOCLAMP-2A in either of the SEVC modes should be quick to question, then adjust, the microelectrode and its placement. The AXOCLAMP-2A is a sophisticated instrument. Even experienced researchers are advised to read this manual thoroughly and to familiarize themselves with the instrument using model electrodes (i.e. resistors) and cells (e.g. parallel RC) before attempting experiments with real microelectrodes and cells.