The role of the N-terminal region of human type 2 ryanodine receptor in intersubunit cross-linking and Ca2+ leak induced by oxidative stress

Abstract

The type 2 ryanodine receptor (RyR2) plays a key role in the cardiac intracellular Ca2+ cycling. We have previously shown that oxidative stress increases the activity of resting RyR2 (leak) by promoting the formation of disulfide bonds between neighboring channel subunits. However, the molecular mechanisms of redox regulation as well as the redox-sensitive sites within human RyR2 (hRyR2) remain largely unknown. It has been suggested that structural integrity of the cytosolic N-terminal region (NTR) is critical for proper RyR2 function.