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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / pharmacology
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Animals
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Calcineurin
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Calcium / physiology*
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Calmodulin-Binding Proteins / physiology*
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Cell Compartmentation
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Cells, Cultured
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Ethers, Cyclic / pharmacology
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Intracellular Fluid / metabolism
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Kinetics
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Marine Toxins
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Microcystins
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Models, Biological
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Neurons / drug effects
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Neurons / physiology*
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Okadaic Acid
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Patch-Clamp Techniques
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Peptides, Cyclic / pharmacology
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Phosphoprotein Phosphatases / physiology*
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Phosphorylation
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Potassium Channels / drug effects
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Potassium Channels / physiology*
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Protein Processing, Post-Translational
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Rana catesbeiana
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Second Messenger Systems
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Sympathetic Nervous System / cytology*
Substances
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Calmodulin-Binding Proteins
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Enzyme Inhibitors
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Ethers, Cyclic
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Marine Toxins
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Microcystins
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Peptides, Cyclic
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Potassium Channels
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Okadaic Acid
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Adenosine Triphosphate
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Calcineurin
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Phosphoprotein Phosphatases
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cyanoginosin LR
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Calcium