Brian Salzberg
University of Pennsylvania

Editor, Channels, Transporters, and Receptors
Biophysical Journal

What has been your most exciting discovery as a biophysicist?

Certainly, my most exciting discovery as a biophysicist was the finding of voltage-sensitive dyes, notably Merocyanine 540, with Larry Cohen and Vicencio Davila in 1972. I still remember the thrill that I experienced when, in the process of assaying fluorescent molecules for voltage sensitivity by applying depolarizing and hyperpolarizing steps to a voltage-clamped squid giant axon and measuring the attendant fluorescence changes, we needed to reduce the oscilloscope gain three clicks to accommodate the fluorescence signal on the oscilloscope screen. This was followed, many years later, by finding, in the course of looking for molecular indicators of membrane potential, that rapid changes in light scattering arising from mammalian nerve terminals in response to the action potential revealed angstrom-scale changes in the terminal diameter.

At a cocktail party of non-scientists, how would you explain what you do?

Very many, if not most, cellular processes depend upon changes in either the voltage across the membrane or rapid changes in intracellular calcium. We discovered how to monitor these events by optical means, introducing molecular indicators of both voltage (potentiometric dyes with Cohen and Davila) and changes in intracellular calcium (first the calcium indicator Arsenazo, with Joel Brown, Paul Deweer, Cohen, and others). Optical techniques tend to be noninvasive, and I have worked to improve these, particularly the use of voltage-sensitive dyes and light scattering.