Single potassium M-channels in rat sympathetic neurons have multiple voltage-dependent kinetic components in their activity: short, medium, and long closed times (τCS, τCM, and τCL) and short and long open times (τOS and τOL). All five components can be detected in cell-attached patches, but only four of them (τCS, τCM, τOS, and τOL) in excised patches (Selyanko and Brown, 1993, J. Physiol. (Lond.). 472:711–724; 1996, Neuron. 16:151–162; 1996, Neuropharmacology. 35:933–947). Analysis of the burst structure of activity recorded from cell-attached and excised inside-out patches showed it to be consistent with the sequential kinetic scheme CL ↔ OS ↔ CM ↔ OL ↔ CS. Using this scheme and experimentally determined kinetic parameters, we successfully simulated the activity of M-channels both under steady-state conditions and during depolarizing voltage steps. Consistent with the characteristic behavior of macroscopic M-current, ensemble currents constructed from simulated M-channels had exponential activation and deactivation, with no delays, when tested in the range between −50 and −20 mV.