Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels

Nat Cell Biol. 2000 Mar;2(3):173-7. doi: 10.1038/35004052.

Abstract

A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for ICa facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent ICa facilitation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • Animals
  • Barium / pharmacology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels, L-Type / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Calmodulin / metabolism
  • Calmodulin / pharmacology
  • Cell Membrane / enzymology
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Feedback
  • Ion Channel Gating / drug effects
  • Mice
  • Myocardium / cytology
  • Myocardium / enzymology*
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects

Substances

  • Calcium Channels, L-Type
  • Calmodulin
  • Enzyme Inhibitors
  • Peptides
  • Barium
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium