Allosteric coupling of RyR calcium channels: Is it relevant to the [patho]physiology of heart and muscle?

This study reveals an examination of the phenomenon of coupled gating between ryanodine receptors, the Ca2+ channels of the sarcoplasmic reticulum of skeletal and cardiac muscle, essential for the execution of contraction upon electrical excitation. It asks whether the phenomenon-pairs of channels or larger groups, reconstituted in bilayers, opening and closing together-reflects allosteric interactions that require contact between channels, and whether the phenomenon occurs in vivo with sufficient prevalence to be relevant to physiology and pathophysiology. The examination covers definitions, observations of coupled currents, structural studies of channels, in purified or in native membranes, and quantitative modeling of the phenomena. It concludes with a negative answer to the question whether a physiological role is proven, but a hopeful perspective on further research.