Single potassium M-channels in rat sympathetic neurons have multiple voltage-dependent kinetic components in their activity: short, medium, and long closed times (tau(CS), tau(CM), and tau(CL)) and short and long open times (tau(OS) and tau(OL)). All five components can be detected in cell-attached patches, but only four of them (tau(CS), tau(CM), tau(OS), and tau(OL)) in excised patches (, 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 C(L) left arrow over right arrow O(S) left arrow over right arrow C(M) left arrow over right arrow O(L) left arrow over right arrow C(S). 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.