Functional nonequality of the cardiac and skeletal ryanodine receptors

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Abstract
Dihydropyridine receptors (DHPRs), which are voltage-gated Ca 2+ channels, and ryanodine receptors (RyRs), which are intracellular Ca 2+ release channels, are expressed in diverse cell types, including skeletal and cardiac muscle. In skeletal muscle, there appears to be reciprocal signaling between the skeletal isoforms of both the DHPR and the RyR (RyR-1), such that Ca 2+ release activity of RyR-1 is controlled by the DHPR and Ca 2+ channel activity of the DHPR is controlled by RyR-1. Dyspedic skeletal muscle cells, which do not express RyR-1, lack excitation–contraction coupling and have an ≈30-fold reduction in L-type Ca 2+ current density. Here we have examined the ability of the predominant cardiac and brain RyR isoform, RyR-2, to substitute for RyR-1 in interacting with the skeletal DHPR. When RyR-2 is expressed in dyspedic muscle cells, it gives rise to spontaneous intracellular Ca 2+ oscillations and supports Ca 2+ entry-induced Ca 2+ release. However, unlike RyR-1, the expressed RyR-2 does not increase the Ca 2+ channel activity of the DHPR, nor is the gating of RyR-2 controlled by the skeletal DHPR. Thus, the ability to participate in skeletal-type reciprocal signaling appears to be a unique feature of RyR-1.