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.
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Vollum Institute, Oregon Health Sciences University, Portland 97201-3098, USA.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin; D002118:Calcium / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000502:physiology*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008387:Marine Toxins; D052998:Microcystins; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011892:Rana catesbeiana; D015290:Second Messenger Systems; D013564:Sympathetic Nervous System / Q000166:cytology*
D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D015221:Potassium Channels; D019319:Okadaic Acid; D000255:Adenosine Triphosphate; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR; D002118:Calcium