Putative roles of type 3 ryanodine receptor isoforms (RyR3)

Ca2+-release from the sarcoplasmic or endoplasmic reticulum, the intracellu lar Ca2+ store, is mediated by the ryanodine receptor (RyR) and/or the inos itol trisphosphate receptor (IP3R). While IP3R. is a ligand(IP3)-operated c hannel RyR can be gated by a ligand (Ca2+) and/or mechanical coupling with the voltage sensor There are three genetically distinct isoforms among RyR in mammals: RyR1-3. RyR1, the primary isoform in the skeletal muscle, can b e gated by direct or indirect coupling with the conformation change of the alpha 1S subunit of dihydropyridine receptor (DHPR) on the T-tubules (trans versely invaginated sarcolemma) upon depolarization of skeletal muscles or by the increased cytoplasmic Ca2+ (Ca2+-induced Ca2+ release, CICR). RyR2, the primary isoform in the cardiac ventricular muscle (and, in a lesser amo unt, the brain), can be gated by Ca2+ which flows in through DHPR, especial ly the alpha 1C subunit on depolarization. RyR3 is distributed ubiquitously in various tissues and may be coexpressed with RyR1 and RyR2. RyR3 is cons idered to be similar to RyR2 in the respect that it can be activated by Ca2 +, in view of the lack of available evidence to show the activation by the alpha 1S subunit. Therefore, it is anticipated that RyR3 might take part th rough CICR in Ca2+ signaling in smooth muscle and other non-muscle cells. T o address the possible involvement of the CICR mechanism in the Ca2+ signal transduction, it is critical to assess the effect of Mg2+ on the CICR acti vity and the cytoplasmic concentration of Mg2+. In this brief review our di scussion focuses on the effects of Ca2+ and Mg2+ on the activity of RyR3. ( Trends Cardiovasc Med 2000;10:65-70). (C) 2000 Elsevier Science Inc.