Ionic channels with conformational substates

Abstract

Recent studies of protein dynamics suggest that ionic channels can assume many conformational substates. Long-lived substates have been directly observed in single-channel current records. In many cases, however, the lifetimes of conformational states will be far below the theoretical limit of time resolution of single-channel experiments. The existence of such hidden substates may strongly influence the observable (time-averaged) properties of a channel, such as the concentration dependence of conductance. A channel exhibiting fast, voltage-dependent transitions between different conductance states may behave as an intrinsic rectifier. In the presence of more than one permeable ion species, coupling between ionic fluxes may occur, even when the channel has only a single ion-binding site. In special situations the rate of ion translocation becomes limited by the rate of conformational transitions, meaning that the channel approaches the kinetic behavior of a carrier. As a result of the strong coulombic interaction between an ion in a binding site and polar groups of the protein, rate constants of conformational transitions may depend on the occupancy of the binding site. Under this condition a nonequilibrium distribution of conformational states is created when ions are driven through the channel by an external force. This may lead to an apparent violation of microscopic reversibility, i.e., to a situation in which the frequency of transitions from state A to state B is no longer equal to the transition frequency from state B to state A.

Optimization and Control of Bilinear Systems

“…Lev et al have concluded that the relaxation rates of some conformational degrees of freedom are comparable or smaller than the frequency of ion jumps in the channel. As Ciani (1984) and Läuger (1985) indicated, there is an appreciable difference between fast and slow conformational motions. Läuger observed that the fast conformational degrees of freedom; that is, the motions whose characteristic times are small compared to the time of an ion jump over the barrier, manage to accommodate themselves to the ion and their role amounts to making the ion "heavier" just as the electron becomes heavier in a crystal when it interacts with lattice vibrations (the polaron effect).…”

Electrogenic properties of the sodium-alanine cotransporter in pancreatic acinar cells: II. Comparison with transport models

“…2), so that the fluxes of N and S are completely coupled. For a discussion of the more general case of arbitrary coupling ratio, see Ciani (1984) andL/iuger (1985). We further assume (as before) that the binding/unbinding reactions at the interface are always in equilibrium.…”

Quantitative description of three modes of activity of fast chloride channels from rat skeletal muscle.

“…A large Cl-conductance is important to stabilize the resting membrane potential, as mammalian muscles with reduced Cl-conductance become hyperexcitable and produce trains of action potentials characteristic of myotonia (Adrian & Bryant, 1974). Using the patch-clamp recording technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981) to explore for channels that might underlie the resting Cl-conductance, we have observed three Cl--selective channels in cultured rat skeletal muscle (Blatz & Magleby, 1983, 1985. One of these channels has a large conductance of 430 pS (symmetrical 143 mM-KCl) but is unlikely to contribute significantly to resting Cl-conductance, because it is closed at resting membrane potentials.…”