Is there something fishy about the regulation of the ryanodine receptor in the fish heart?

The fish cardiac sarcoplasmic reticulum (SR) holds large quantities of Ca, however, Ca-induced Ca-release (CICR) is weak in these myocytes and contraction and relaxation is largely determined by transsarcolemmal Ca flux. Additionally, many fish species live in a cold and seasonally variable thermal habitat which could provide challenges to regulation of excitation-contraction (EC) coupling. Here, we focus on the cardiac SR Ca release channel (RyR2) in fish and ask whether it may be regulated differently from mammalian RyR2. We review data indicating that fish RyR2s occur in lower density, are more spatially separated within the SR membrane, and are less responsive to cytosolic [Ca] than mammalian RyR2 channels. All of these features would contribute to the weak CICR evident from functional studies. We also consider how CICR can be enhanced in fish myocytes following β-adrenergic stimulation and application of low levels of caffeine, and how acute and chronic temperature change may affect the gating properties of fish RyR2s. It is clear that a lack of insight into the fundamental gating and conductance properties of fish RyR2 channels is hindering our understanding of the role of the SR in fish cardiac EC coupling. We conclude by reflecting on how studies which probe the biophysical properties of fish RyR2 channel gating in response to various ligands and temperatures would be very instructive in understanding the role of the SR in the evolution of the heart.