Differences in both inositol 1,4,5-trisphosphate mass and inositol 1,4,5-trisphosphate receptors between normal and dystrophic skeletal muscle cell lines

✍ Scribed by Jose L. Liberona; Jeanne A. Powell; Sheela Shenoi; Lee Petherbridge; Raul Caviedes; Enrique Jaimovich

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 354 KB
• Volume: 21
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/(sici)1097-4598(199807)21:7<902::aid-mus8>3.0.co;2-a

✦ Synopsis

Human normal (RCMH) and Duchenne muscular dystrophy (RCDMD) cell lines, as well as newly developed normal and dystrophic murine cell lines, were used for the study of both changes in inositol 1,4,5trisphosphate (IP 3 ) mass and IP 3 binding to receptors. Basal levels of IP 3 were increased two-to threefold in dystrophic human and murine cell lines compared to normal cell lines. Potassium depolarization induced a timedependent IP 3 rise in normal human cells and cells of the myogenic mouse cell line (129CB3), which returned to their basal levels after 60 s. However, in the human dystrophic cell line (RCDMD), IP 3 levels remained high up to 200 s after potassium depolarization. Expression of IP 3 receptors was studied measuring specific binding of 3 H-IP 3 in the murine cell lines (normal 129CB3 and dystrophic mdx XLT 4-2). All the cell lines bind 3 H-IP 3 with relatively high affinity (K d : between 40 and 100 nmol/L). IP 3 receptors are concentrated in the nuclear fraction, and their density is significantly higher in dystrophic cells compared to normal. These findings together with high basal levels of IP 3 mass suggest a possible role for this system in the deficiency of intracellular calcium regulation in Duchenne muscular dystrophy.