EXPRESSION OF MUSCLE-TYPE PHOSPHORYLASE IN INNERVATED AND ANEURAL CULTURED MUSCLE OF PATIENTS WITH MYOPHOSPHORYLASE DEFICIENCY

Patients with McArdle's myopathy lack muscle glycogen phosphorylase (M -GP) activity. Regenerating and cultured muscle of patients with McArd le's myopathy presents a glycogen phosphorylase (GP) activity, but it is not firmly established whether M-GP or non-M-GP isoforms are expres sed. We have cultured myoblasts from biopsy specimen of five patients with McArdle's myopathy. Skeletal muscle was cultured aneurally or was innervated by coculture with fetal rat spinal cord explants. In the p atients' muscle biopsies and in their cultured innervated and aneural muscle we studied total GP activity, isoenzymatic pattern, reactivity with anti-M-GP antiserum, and presence of M-GP mRNA. There was no dete ctable enzymatic activity, no immunoreactivity with anti-M-GP antiseru m, and no M-GP mRNA in the muscle biopsy of all patients. GP activity, M-GP isozyme, and anti-M-GP antiserum reactivity were present in pati ents' aneural cultures, increased after innervation, and were undistin guishable from control. M-GP mRNA was demonstrated in both aneural and innervated cultures of patients and control by primer extension and P CR amplification of total RNA. Our studies indicate that the M-GP gene is normally transcribed and translated in cultured muscle of patients with myophosphorylase deficiency.