title: Activator-induced dynamic disorder and molecular memory in human two-pore domain hTREK1 K channel.
abstract: Ion channels are fundamental molecules in the nervous system that catalyze the flux of ions across the cell membrane. Ion channel flux activity is comparable to the catalytic activity of enzyme molecules. Saturating concentrations of substrate induce "dynamic disorder" in the kinetic rate processes of single-enzyme molecules and consequently, develop correlative "memory" of the previous history of activities. Similarly, binding of ions as substrate alone or in presence of agonists affects the catalytic turnover of single-ion channels. Here, we investigated the possible existence of dynamic disorder and molecular memory in the single human-TREK1-channel due to binding of substrate/agonist using the excised inside-out patch-clamp technique. Our results suggest that the single-hTREK1-channel behaves as a typical Michaelis-Menten enzyme molecule with a high-affinity binding site for K(+) ion as substrate. But, in contrast to enzyme, dynamic disorder in single-hTREK1-channel was not induced by substrate K(+) binding, but required allosteric modification of the channel molecule by the agonist, trichloroethanol. In addition, interaction of trichloroethanol with hTREK1 induced strong correlation in the waiting time and flux intensity, exemplified by distinct mode-switching between high and low flux activities. This suggested the induction of molecular memory in the channel molecule by the agonist, which persisted for several decades in time. Our mathematical modeling studies identified the kinetic rate processes associated with dynamic disorder. It further revealed the presence of multiple populations of distinct conformations that contributed to the "heterogeneity" and consequently, to the molecular memory phenomenon that we observed.
  
  
  BACKGROUND
  The online version of this article (doi:10.1007/s12154-010-0053-3) contains supplementary material, which is available to authorized users.
authors.forename: Tapan Kumar
authors.initials: TK
authors.lastname: Nayak
authors.forename: Saswati
authors.initials: S
authors.lastname: Dana
authors.forename: Soumyendu
authors.initials: S
authors.lastname: Raha
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Sikdar