The Ryanodine Receptor (RyR) intracellular calcium release channels (CRC) regulate release of calcium from intracellular stores in the ER/SR. Though expressed in many cell types, they are best known for their roles in muscle contraction; indeed loss-of-function mutations are associated with myopathy in humans. We propose this narrow view of the RyR function fails to account for the full range of phenotypes observed in humans carrying RYR1 mutations, which include slow muscle cell defects. We are interested in understanding how each of the ryrs contributes to development and behavior. We have generated null ryr mutants in each of the genes that contribute to skeletal muscle function in zebrafish. Our results show ryr1a appears to be specific to slow muscle fibers, while ryr1b and 3 seem to be fast muscle specific. Surprisingly, both ryr1a and ryr3 are dispensable, and we are interested in how calcium release during muscle contraction and behavior are affected. We have used GCaMP6 to visualize calcium fluctuations in both slow and fast muscle fibers for null ryr mutants. Muscle contractions are electrically stimulated and imaged using a SPIM microscope. Behavioral assays have also been used to characterize the phenotypes of single and combinations of ryr mutants. Our preliminary results indicate: First, animals lacking the RyR isoform specific to slow muscle fibers have no functional slow muscle, exhibit altered movement behaviors as embryos and adults, and are fully viable in the laboratory. This has given us a probe to investigate the role of this subset of muscle. Second, ryr mutants have defects in muscle cell differentiation in addition to defects in muscle contraction. Third, triple mutants that are completely paralyzed have distinct malformations in craniofacial development that are wholly secondary to loss of muscle contractility.