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Calcineurin regulates M channel modal gating in sympathetic neurons
1Vollum Institute, Oregon Health Sciences University, Portland 97201-3098, USA.
Abstract:
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.
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