Alendronate affects calcium dynamics in cardiomyocytes in vitro

Area of Science:

• Cardiology
• Pharmacology
• Cell Biology

Background:

• Bisphosphonates, like alendronate (ALN), are standard osteoporosis treatments.
• Emerging evidence links bisphosphonate use to increased risk of serious atrial fibrillation (AF).
• The underlying mechanism for this cardiovascular side effect remains unclear.

Purpose of the Study:

• To investigate the effects of alendronate (ALN) on cardiomyocyte calcium homeostasis.
• To explore how ALN influences protein isoprenylation in cardiac cells.
• To elucidate the cellular mechanisms potentially linking ALN to atrial fibrillation.

Main Methods:

• In vitro study using atrial and ventricular cardiomyocytes.
• Acute and long-term (48h) exposure to varying concentrations of ALN.
• Analysis of intracellular calcium dynamics via fluorescence measurements and Western blotting of calcium-regulating proteins.
• Assessment of protein farnesylation.

Main Results:

• ALN treatment impaired calcium responses to caffeine in both atrial and ventricular cells.
• Long-term ALN exposure induced calcium oscillations and altered caffeine responses specifically in atrial cardiomyocytes.
• These calcium dynamics changes correlated with altered expression of key calcium-regulating proteins.
• ALN showed minimal impact on protein isoprenylation in cardiomyocytes.

Conclusions:

• Alendronate induces calcium handling abnormalities in atrial cardiomyocytes.
• These ALN-induced changes promote pacemaker-like cellular behavior.
• This mechanism may explain the increased risk of atrial fibrillation associated with bisphosphonate therapy.