Lanthanides do not function as calcium analogues in scallop myosin

Area of Science:

• Biochemistry
• Muscle Physiology
• Bioinorganic Chemistry

Background:

• Lanthanides are frequently investigated as calcium (Ca²⁺) analogues in biological systems due to similar ionic radii.
• Understanding the interaction of lanthanides with muscle proteins is crucial for elucidating calcium's role in muscle contraction.
• Regulatory myosins, found in both thick and thin filaments, are key targets for studying calcium-dependent processes.

Purpose of the Study:

• To investigate whether lanthanides (terbium, gadolinium, europium) function as calcium analogues in the actin-activated ATPase of regulated myosins.
• To determine the concentration-dependent activation profiles of myosins by different lanthanide ions.
• To clarify the mechanism behind lanthanide-induced activation in scallop and rabbit skeletal muscle systems.

Main Methods:

• Enzyme kinetic assays measuring ATPase activity of scallop adductor myosin and rabbit skeletal muscle myosin.
• Titration experiments using varying concentrations of terbium (Tb(III)), gadolinium (Gd(III)), and europium (Eu(III)).
• Analysis of lanthanide interaction with the calcium-specific regulatory sites on myosin and associated proteins.

Main Results:

• Scallop myosin initially showed apparent activation by lanthanides, but activity rapidly declined at higher concentrations.
• Contrary to expectations, lanthanides did not compete with calcium for the calcium-binding site in scallop myosin.
• The observed lanthanide activation was identified as an artifact due to trace calcium release from chelators during titration.

Conclusions:

• Lanthanides do not serve as calcium analogues in the scallop myosin system under these experimental conditions.
• The activation observed in lanthanide titrations is an artifact, not a true functional mimicry of calcium.
• The role of lanthanides in activating troponin:tropomyosin systems requires further rigorous investigation, as their ability to do so is questionable.