Current noise reveals protonation kinetics and number of ionizable sites in an open protein ion channel

In analogy to current fluctuations found in solid state electronic microstructure devices, excess noise generated by the reversible ionization of sites in a transmembrane ionic channel was observed. By analyzing the pH-dependent fluctuations in the current through fully open single channels formed by the {α}-toxin protein, we were able to evaluate the protonation rate constants, the number of sites participating in the protonation process, and the effect of recharging a single site on the channel conductance.