Heavy metal-induced Ca2+ release from sarcoplasmic reticulum

Area of Science:

• Biochemistry
• Cell Biology
• Muscle Physiology

Background:

• The sarcoplasmic reticulum (SR) is crucial for calcium (Ca2+) regulation in muscle cells.
• Heavy metals can disrupt cellular processes, including Ca2+ handling by the SR.
• Understanding Ca2+ release mechanisms is vital for comprehending muscle function.

Purpose of the Study:

• To investigate the distinct mechanisms of heavy metal-induced Ca2+ release from isolated sarcoplasmic reticulum vesicles.
• To determine the role of sulfhydryl oxidation in these Ca2+ release processes.
• To assess the physiological relevance of sulfhydryl oxidation in skeletal muscle excitation-contraction coupling.

Main Methods:

• Utilized isolated sarcoplasmic reticulum vesicles to study Ca2+ release.
• Investigated heavy metal (silver, mercurials) effects on Ca2+ release.
• Examined the influence of ruthenium red, glutathione, and dithiothreitol (DTT) on Ca2+ release.
• Assessed the impact of DTT and glutathione on excitation-contraction coupling in intact muscle fibers.

Main Results:

• Identified two distinct forms of heavy metal-induced Ca2+ release: one ruthenium red-sensitive and localized, the other ruthenium red-insensitive and widespread.
• Both Ca2+ release forms were inhibited by glutathione and DTT, suggesting a role for sulfhydryl oxidation.
• In intact muscle fibers, DTT and glutathione did not significantly affect excitation-contraction coupling.
• Heavy metal-induced Ca2+ release was not solely a consequence of sarcoplasmic reticulum Ca2+ pump inhibition.

Conclusions:

• Heavy metals induce Ca2+ release via at least two distinct pathways in the sarcoplasmic reticulum.
• While sulfhydryl oxidation can inhibit these releases in vitro, it is not physiologically essential for skeletal muscle excitation-contraction coupling.
• These findings differentiate direct heavy metal effects on Ca2+ channels/pumps from broader cellular impacts.