Ryanodine receptor Ca2+ release channels: does diversity in form equal diversity in function?

Abstract

Complexities in calcium signaling in eukaryotic cells require diversity in the proteins involved in generating these signals. In this review, we consider the ryanodine receptor (RyR) family of intracellular calcium release channels. This includes species, tissue, and cellular distributions of the RyRs and mechanisms of activation, deactivation, and inactivation of RyR calcium release events. In addition, as first observed in nonmammalian vertebrate skeletal muscles, it is now clear that more than one RyR isoform is frequently coexpressed within many cell types. How multiple ryanodine receptor release channels are used to generate intracellular calcium transients is unknown. Therefore, a primary focus of this review is why more than one RyR is required for this purpose, particularly in a tissue, such as vertebrate fast-twitch skeletal muscles, where a relatively simple and straightforward change in calcium would appear to be required to elicit contraction. Finally, the roles of the RyR isoforms and the calcium release events they mediate in the development of embryonic skeletal muscle are considered.

Functional Characterization of the Recombinant Type 3 Ca2+ Release Channel (Ryanodine Receptor) Expressed in HEK293 Cells

“…Perchlorate is able to activate the cloned RyR3. These single channel properties of the cloned RyR3 are similar to those of the recombinant RyR1 (58) and the native RyR1 (1)(2)(3)(4)(5)41).…”

“…The bovine RyR1 was stained by monoclonal antibody 34C (lane 1). This monoclonal antibody recognizes both the chicken ␣ and ␤ RyR isoforms that are homologues of the mammalian RyR1 and RyR3, respectively (5,39). The cloned RyR3 and bovine diaphragm RyR3 migrated similarly but slightly faster than the bovine diaphragm RyR1, similar to those reported previously (7).…”

“…the products of different genes and share 66 -70% amino acid sequence identity (1)(2)(3)(4)(5). Earlier studies using RNA blot analysis revealed that the expression patterns of these isoforms were very different (6).…”

“…On the other hand, little is known about the physiological role, regulation, and channel properties of the RyR3 isoform (5). Isolation and biochemical and biophysical characterization of RyR3 have been impeded by its low abundance and its coexpression with other RyR isoforms.…”

Ligand-gated Ion Channels

“…These RyR channels are ubiquitously expressed in many types of cells and participate in a variety of important Ca 2+ signaling phenomena (neurotransmission, secretion, etc.). In addition to the three mammalian isoforms described below, various nonmammalian isoforms of the ryanodine receptor have been identified and these are discussed in Sutko and Airey (1996). The function of the ryanodine receptor channels may also be influenced by closely associated proteins such as the tacrolimus (FK506)-binding protein, calmodulin (Yamaguchi et al, 2003) The modulators of channel function included in this table are those most commonly used to identify ryanodine-sensitive Ca 2+ release pathways.…”