کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2574453 1561274 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Alendronate affects calcium dynamics in cardiomyocytes in vitro
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Alendronate affects calcium dynamics in cardiomyocytes in vitro
چکیده انگلیسی

Therapy with bisphosphonates, including alendronate (ALN), is considered a safe and effective treatment for osteoporosis. However, recent studies have reported an unexpected increase in serious atrial fibrillation (AF) in patients treated with bisphosphonates. The mechanism that explains this side effect remains unknown. Since AF is associated with an altered sarcoendoplasmic reticulum calcium load, we studied how ALN affects cardiomyocyte calcium homeostasis and protein isoprenylation in vitro. Acute and long-term (48 h) treatment of atrial and ventricular cardiomyocytes with ALN (10− 8–10− 6 M) was performed. Changes in calcium dynamics were determined by both fluorescence measurement of cytosolic free Ca2+ concentration and western blot analysis of calcium-regulating proteins. Finally, effect of ALN on protein farnesylation was also identified. In both atrial and ventricular cardiomyocytes, ALN treatment delayed and diminished calcium responses to caffeine. Only in atrial cells, long-term exposure to ALN-induced transitory calcium oscillations and led to the development of oscillatory component in calcium responses to caffeine. Changes in calcium dynamics were accompanied by changes in expression of proteins controlling sarcoendoplasmic reticulum calcium. In contrast, ALN minimally affected protein isoprenylation in these cells. In summary, treatment of atrial cardiomyocytes with ALN-induced abnormalities in calcium dynamics consistent with induction of a self-stimulatory, pacemaker-like behavior, which may contribute to the development of cardiac side effects associated with these drugs.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vascular Pharmacology - Volume 51, Issues 5–6, November–December 2009, Pages 350–358
نویسندگان
, , , , , , ,