Figure 2.

(A) Proposed transmembrane arrangements for the RyR showing two possible orientations for the luminal loop between M3 and M4. If this loop is located in the lumen, it may be a site of interaction with triadin, and by extension with calsequestrin. Conversely, if the loop dips back into the membrane, it may form either a part of the conduction pathway or ion selectivity filter. (B) Sequence comparison of the proposed pore region. The sequence for the loop between M3 and M4 is given for the human skeletal RyR1 isoform, as well as the residues that are conserved between RyR subtypes, the conserved sequence for the related IP₃Rs, locations for amino acids that are identical between all RyR and IP₃R subtypes, and the analogous residues in the selectivity filter of the S. lividans K⁺ channel.