A brief communication investigating the role of inhibitor-1, a modulator of protein phosphatase 1 (PP1), in the regulation of the cardiac ryanodine receptor type-2 (RyR2) channel appeared online today. The work from the group of Dr. Stefan Neef, University of Regensburg, Germany, to which we contributed, demonstrates that I-1 acutely modulates the activity of the calcium/calmodulin-dependent kinase II (CaMKII) by regulating PP1 activity. However, although ablation of I-1 should thus limit CaMKII-activation, CaMKII activity was exaggerated under β-adrenergic stress upon chronic loss of I-1 in knockout mice. Experimental and computational studies suggest that this is due to chronic upregulation of the exchange protein activated by cAMP (EPAC), leading to augmented CaMKII activation.

Neef S, Heijman J, Otte K, Dewenter M, Saadatmand A. R, Meyer-Roxlau S, Antos C. L, Backs J, Dobrev D, Wagner M, Maier L. S, El-Armouche A (2017) Chronic loss of inhibitor-1 diminishes cardiac RyR2 phosphorylation despite exaggerated CaMKII activity. Naunyn Schmiedeberg’s Arch Pharmacol, Epub. [Pubmed]