Multiple kinetic states underlying macroscopic M-currents in bullfrog sympathetic neurons

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Abstract
M-current is a time- and voltage-dependent potassium current which is suppressible by muscarinic receptor activation. We have used curve fitting and noise analysis to determine if macroscopic M-currents deviate from a previously predicted simple two-state kinetic scheme. The M-current was best described by three kinetically distinct components: `fast' ($\tau _{0}$), `intermediate' ($\tau _{1}$) and `slow' ($\tau _{2}$) time constants. The `fast' ($\tau _{0}$) and `intermediate' ($\tau _{1}$) components were identified from the spectra of M-current noise at potentials positive to the cells' resting membrane potential. The `intermediate' ($\tau _{1}$) and `slow' ($\tau _{2}$) components were seen by curve fitting M-current deactivation currents. The `intermediate' ($\tau _{1}$) time constant was voltage dependent (decreasing e-fold in 23 mV), but voltage dependence of the `fast' ($\tau _{0}$) and `slow' ($\tau _{2}$) components was not obvious. All kinetic components were sensitive to muscarine, with the `intermediate' ($\tau _{1}$) and `slow' ($\tau _{2}$) being equally so. These data suggest that all components may derive from the same channel population, and that the M-channel may have at least four kinetic states.