Altered calcium signaling in platelets from bile-duct-ligated rats

Noemí M. Atucha , David Iyú , Antonia Alcaraz , Vladimir Rosa , Concepción Martínez-Prieto , M. Clara Ortiz , Juan Antonio Rosado , Joaquín García-Estañ , Joaquín García-Estañ (1)

1 Universidad de Murcia

Background/Aims: we have analyzed the mechanisms of calcium entry and release in platelets obtained from bile duct-ligated rats (BDL), two (cholestasis group) and four weeks after surgery. Methods: platelets were washed and loaded with fura-2. Cytosolic calcium concentration ([Ca2+] i}) was determined in cell suspensions by means of fluorescence spectroscopy. Results: Basal [Ca2+] i} was similar in platelets from BDL rats as compared with those from their respective controls, both in the absence and presence of extracellular calcium. Platelet stimulation with thrombin in the absence and presence of extracellular calcium induced a rapid rise in [Ca2+] i} that was of greater magnitude in platelets from BDL rats than in controls. Calcium storage was significantly elevated in platelets from BDL rats, as well as the activity of the sarcoendoplasmic reticulum calcium ATP-ase (SERCA). Capacitative calcium entry, as evaluated by inhibition of SERCA with thapsigargin, is also altered in platelets from BDL rats, showing lower rates of calcium entry. Conclusions: chronic BDL alters intracellular calcium homeostasis in platelets, so that an enhanced calcium release is evoked by thrombin, which may be due to an increased amount of calcium stored in the intracellular organelles and secondary to an enhanced activity of SERCA. These alterations are already evident before cirrhosis is completely developed, during the cholestasis phase.

Mots clés: Medicine

Noemí M. Atucha, David Iyú, Antonia Alcaraz, Vladimir Rosa, Concepción Martínez-Prieto, et al.. Altered calcium signaling in platelets from bile-duct-ligated rats. Clinical Science, 2006, 112 (3), pp.167-174. ⟨10.1042/CS20060226⟩. ⟨hal-00479341⟩