Calcineurin Regulates M Channel Modal Gating in Sympathetic Neurons

The M current regulates neuronal excitability, with its amplitude resulting from high open probability modal M channel behavior. The M current is affected by changing intracellular calcium levels. It is proposed that internal calcium acts by regulating M channel modal gating. Intracellular application of a preactivated form of the calcium-dependent phosphatase calcineurin (CaN420) inhibited the macroscopic M current, while its application to excised inside-out patches reduced high open probability M channel activity. Addition of ATP reversed the action of CaN420 on excised patches. The change in M channel gating induced by CaN420 was different from the effect of muscarine. A kinetic model supports the proposition that shifts in channel gating induced by calcium-dependent phosphorylation and dephosphorylation control M current amplitude.