Adenylate cyclase in muscular dystrophy

Area of Science:

• Biochemistry
• Cell Biology
• Muscle Physiology

Background:

• Adenylate cyclase activity differences were previously noted in normal vs. dystrophic chick muscle sarcolemma.
• The role of sarcoplasmic reticulum (SR) adenylate cyclase and its relation to muscular dystrophy pathophysiology remain unclear.

Purpose of the Study:

• To investigate adenylate cyclase activity in SR of normal and dystrophic chick muscles.
• To explore the link between adenylate cyclase changes and muscular dystrophy.
• To examine if findings extend to Duchenne human muscular dystrophy (DMD) by analyzing erythrocyte ghosts.

Main Methods:

• Microsomal separation from pectoralis muscles of normal and dystrophic chickens.
• Enzyme kinetic analysis of adenylate cyclase and ATPase activities.
• Calcium uptake and binding assays.
• Subcellular fractionation and histochemical studies.

Main Results:

• Dystrophic muscles showed higher microsomal yields and elevated adenylate cyclase activity, increasing with disease progression.
• Calcium did not affect MgATP2- cooperativity but inhibited the enzyme; magnesium competitively removed inhibition and stimulated activity.
• No differences in calcium uptake were observed; however, dystrophic microsomes had lower kd for Ca2+.
• Adenylate cyclase activity was inversely related to calcium-accumulating activity in SR fractions.

Conclusions:

• Elevated adenylate cyclase in dystrophic muscles is not linked to microsomal calcium accumulation.
• Findings suggest rises in adenylate cyclase and Na+, K+-ATPase are compensatory changes in avian dystrophy.
• These changes may be triggered by a defect in excitation-contraction coupling at the calcium release step.