Markov kinetic schemes.

In the simplest 2-state kinetics (A), a single channel can be in one of two configurations with only one of them associated to a non-zero conductance (filled grey circle). The kinetic parameters and are rates, as they represent the transition probabilities between states, expressed per time unit. In a more general case, single-channel kinetics is described by an -state scheme. Voltage-gated fast-inactivating sodium (B) and delayed-rectifier potassium channels (C) are two examples, where only one state corresponds to a non-zero channel conductance (filled grey circle). An alternative model for sodium channels (D) (Vandenberg and Bezanilla, 1991) is also shown for comparison. We point out that our method can be applied to any kind of kinetic schemes, where the transition rates are known. For (B–C), each state is identified by an arbitrary name convention (, , , etc.), referring to the underlying mapping of these 8- and 5-state channels into multiple 2-state gated subunits (panel E). Indeed, some -state kinetic schemes may be mapped into, or experimentally identified as, a set of independent 2-state gates: the open state of the full scheme corresponds to all the elementary gates in the open states, simultaneously. For instance, the kinetic scheme (B) could be mapped into a set of four independent 2-state gates (E) (i.e., the familiar activation gates and the inactivation gate of sodium fast-inactivating currents), three of whom are identical.