General Characteristics of the Voltage Clamp Technique

The most commonly used method is called the on-cell or cell-attached configuration, because ion channels can be recorded on an intact cell (Jackson 1993). This mode is well suited for investigation of ion channels, which are activated by hormonal stimulation and triggered by intracellular second messengers. 

Another versatile mode is the cell-excised configuration (Hamill 1993). It is obtained by suddenly removing the patch-pipette from the cell, so that the membrane patch is pulled off the cell. This mode easily allows to expose the channel proteins to drugs by changing the bath solution. The single channel currents are recorded on a videotape and are analyzed off-line by a computer system. Various parameters are evaluated, such as the single channel conductance, open-and closed-times of the channel, and the open-state probability, which is the percentage of time the channel stays in its open state. 

Besides these modes, which enable the recording of single channel currents, it is also possible to measure the current flowing through the entire cell. This whole-cell mode is obtained by rupturing the membrane patch in the cell-attached mode (Hamill et al. 1981 Dietzel et al. 1993). This is achieved by applying suction to the interior of the patch-pipette. The whole-cell mode not only allows to record the electrical current, but also to measure the cell potential. Moreover, the cell interior is dialyzed by the electrolyte solution filled into the patch-pipette. 

The fabrication of patch clamp pipettes has been described (Sakmann and Neher 1983 Corey and Stevens 1983 Cavalie et al. 1993). 

Variations of the patch-clamp technique have been used for studying neurotransmitter transduction mechanisms (Smith 1995). 

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