Probing of glutamate receptors at sub-millisecond time scale is a key element needed for understanding of their response kinetics, neural signal transduction, and, in a wider context, intercellular cross talk. One of the classical techniques used to obtain this type of data in electrophysiology is placing a recording pipette in front of a double-barrel solution application pipette, which provides a rapid switch between two solutions. Here we describe a modification of this classical technique, which utilizes a solution application pipette with several loading capillaries. Such a system is capable of replacing multiple application solutions within 7-12 s time intervals. This modified protocol enables ultrafast application of several solutions at the same set of receptors, thus allowing powerful paired-sample statistical approaches. In addition, the same experimental equipment fabricated for the ultra-resolution probing of receptor kinetics can also be applied in several other types of electrophysiological experiments.
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