A final level of analysis to be discussed is one directed at assessing the response of individual ionic channels in the membrane of a neuron. Actually, this technique may be described more as a type of high-resolution extracellular recording. In this method, a glass pipette with a comparatively large tip is drawn, and the tip is fire-polished until it is very smooth. The electrode tip is then placed against the membrane surface of a neuron under visual control. Typically, the neuronal membrane is first cleaned of debris with a jet of fluid to permit a tight seal between the electrode and the membrane. A small suction is then applied to the pipette to tighten its seal with the membrane. Because such an attachment provides a high-resistance junction with the membrane, the minute transmembrane currents that are generated as a result of the opening and closing of individual ionic channels may be monitored. The biophysical characteristics (e.g., open time, inactivation rate) of specific ion channels and how they may be modified by drugs applied via the pipette lumen or to other regions of the neuron being studied can be determined.
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