Non-Markovian stochastic resonance: three-state model of ion channel gating.

Stochastic resonance in single voltage-dependent ion channels is investigated within a three-state non-Markovian modeling of the ion channel conformational dynamics. In contrast to a two-state description one assumes the presence of an additional closed state for the ion channel which mimics the manifold of voltage-independent closed subconformations (inactivated "state"). The conformational transition into the open state occurs through a domain of voltage-dependent closed subconformations (closed "state"). At distinct variance with the standard two-state and also the three-state Markovian approach, the inactivated state is characterized by a broad, nonexponential probability distribution of corresponding residence times. The linear response to a periodic voltage signal is determined for arbitrary distributions of the channel's recovery times. Analytical results are obtained for the spectral amplification of the applied signal and the corresponding signal-to-noise ratio. Alternatively, these results are also derived by use of a corresponding two-state non-Markovian theory which is based on driven integral renewal equations [I. Goychuk and P. Hänggi, Phys. Rev. E 69, 021104 (2004)]. The non-Markovian features of stochastic resonance are studied for a power law distribution of the residence time intervals in the inactivated state which exhibits a large variance. A comparison with the case of biexponentially distributed residence times possessing the same mean value, i.e., the simplest non-Markovian two-state description, is also presented.