CA2+-INDUCED CA2+ RELEASE IN MYOCYTES FROM DYSPEDIC MICE LACKING THE TYPE-1 RYANODINE RECEPTOR

While subtypes 1 and 2 of the ryanodine receptor (RyR) function as intracellular Ca2+ release channels, little is known about the function of the third subtype (RyR-3), first identified in brain, Myocytes from mice homozygous for a targeted mutation in the RyR-1 gene (dyspedic mice) can now be used for a study on the function of RyR-3, which is predominantly expressed in these cells according to our reverse transcription-polymerase chain reaction analysis, We here demonstrate in these myocytes caffeine-, ryanodine- and adenine nucleotide-sensitive Ca2+-induced Ca2+ release with similar to 10 times lower sensitivity to Ca2+ than that of RyR-1. Although RyR-3 does not mediate excitation-contraction coupling of the skeletal muscle type, we propose that RyR-3 may induce intracellular Ca2+ release in response to a Ca2+ rise with a high threshold.