The distal C terminus of the dihydropyridine receptor β 1a subunit is essential for tetrad formation in skeletal muscle

Abstract

Significance Vertebrate skeletal muscle excitation–contraction coupling (ECC) is based on Ca 2+ -influx–independent interchannel cross-talk between DHPR and RyR1. The skeletal muscle DHPR complex consists of the main, voltage-sensing, and pore-forming α 1S subunit, the auxiliary β 1a , α 2 δ-1, γ 1 subunits, and Stac3. The DHPRβ 1a subunit plays an essential role in full triad targeting of DHPRα 1S , voltage sensing, and tetrad formation (grouping of four DHPRs)—the three prerequisites for skeletal muscle ECC. Hence, a lack of DHPRβ 1a results in a lethal phenotype in both β 1 -null mice and zebrafish. Here, we identified the nonconserved, distal C terminus of DHPRβ 1a as playing a pivotal role in the formation of DHPR tetrads, and thus allosteric DHPR–RyR1 coupling, essential for proper skeletal muscle ECC.