Physical interaction between calcineurin and Cav3.2 T-type Ca2+ channel modulates their functions

FEBS Lett. 2013 Jun 19;587(12):1723-30. doi: 10.1016/j.febslet.2013.04.040. Epub 2013 May 10.

Abstract

Cav3.2 T-type Ca(2+) channel is required for the activation of calcineurin/NFAT signaling in cardiac hypertrophy. We aimed to investigate how Cav3.2 and calcineurin interact. We found that Ca(2+) and calmodulin modulate the Cav3.2/calcineurin interaction. Calcineurin binding to Cav3.2 decreases the enzyme's phosphatase activity and diminishes the channel's current density. Phenylephrine-induced hypertrophy in neonatal cardiac myocytes is reduced by a cell-permeable peptide with the calcineurin binding site sequence. These data suggest that Cav3.2 regulates calcineurin/NFAT pathway through both the Ca(2+) influx and calcineurin binding. Our findings unveiled a reciprocal regulation of Ca(2+) signaling which contributes to our understanding of cardiac hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcineurin / metabolism*
  • Calcineurin Inhibitors
  • Calcium / metabolism
  • Calcium Channels, T-Type / chemistry
  • Calcium Channels, T-Type / metabolism*
  • Calmodulin / metabolism
  • Electric Conductivity
  • HEK293 Cells
  • Humans
  • NFATC Transcription Factors / metabolism
  • Protein Binding
  • Rats

Substances

  • CACNA1H protein, human
  • Calcineurin Inhibitors
  • Calcium Channels, T-Type
  • Calmodulin
  • NFATC Transcription Factors
  • Calcineurin
  • Calcium