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

Cav3.2 T-type Ca2+ 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 Ca2+ 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 Ca2+ influx and calcineurin binding. Our findings unveiled a reciprocal regulation of Ca2+ signaling which contributes to our understanding of cardiac hypertrophy.