Nonequilibrium response spectroscopy of voltage-sensitive ion channel gating.

摘要: We describe a new electrophysiological technique called nonequilibrium response spectroscopy, which involves application of rapidly fluctuating (as high as 14 kHz) large-amplitude voltage clamp waveforms to ion channels. As consequence the irreversible (in sense Carnot) exchange energy between field and channel protein, gating is exquisitely sensitive features kinetics that are difficult or impossible adequately resolve by means traditional stepped potential protocols. Here we focus on dichotomous (telegraph) noise fluctuations, broadband Markovian colored fluctuates two values. Because Markov kinetic models can be embedded within higher-dimensional take into account effects many channels calculated algebraically. This makes its generalizations uniquely suitable for model selection analysis. Although macroscopic ionic current measurements, method also applied single recording techniques. show how data from human cardiac isoform (hH1a) Na+ expressed in mammalian cells acquired analyzed, these reveal hidden aspects molecular not revealed conventional methods.