ABSTRACT

The study of electrical signaling and excitability of tissues can be traced back to the 19th century [Ho¨ber, 1905 (1) as quoted by Hille (2)]. It took more than 50 years of study to develop a comprehensive model to describe membrane electrical circuits,(2-5) and another 20 years to voltage-clamp a loose patch (6). Ten years after the invention of the voltage-clamp technique, a gigaohm seal was finally achieved, which allowed high-fidelity recordings of the activity of a single molecule in a patch of cell membrane: single-channel currents (7,8). After more than a century of study, the invention of the microchip-based electrode finally enabled automation of the voltage-clamp technique, thus bringing about a new revolution in the study of ion channels.