Altered Ca2+ handling by ryanodine receptor and Na+-Ca2+ exchange in the heart from ovariectomized rats: role of protein kinase A

Our previous study has demonstrated that ovariectomy (Ovx) significantly increased the left ventricular developed pressure (LVDP) and the maximal rate of developed pressure over time (±dP/dtmax) in the isolated perfused rat heart and the effects were reversed by female sex hormone replacement. In the present investigation, we studied the effects of Ovx for 6 wk on Ca2+ homeostasis that determines the contractile function. Particular emphasis was given to Ca2+ handling by ryanodine receptor (RyR) and Na+-Ca2+ exchange (NCX). 45Ca2+ fluxes via the RyR, NCX, and Ca2+-ATPase (SERCA) were compared with their expression in myocytes from Ovx rats with and without estrogen replacement. Furthermore, we correlated the handling of Ca2+ by these Ca2+ handling proteins with the overall Ca2+ homeostasis by determining the Ca2+ transients induced by electrical stimulation and caffeine, which reveals the dynamic changes of cytosolic Ca2+ concentration ([Ca2+]i) in the heart. In addition, we determined the expression and ...