Ovariectomy enhances SR Ca2+ release and increases Ca2+ spark amplitudes in isolated ventricular myocytes

This study compared Ca2+ homeostasis in ventricular myocytes from 8-month-old female C57BL/6J mice that had either a bilateral ovariectomy (OVX) or a sham surgery at 3 weeks of age. Cells were loaded with fura-2 and field-stimulated or voltage-clamped with steps to membrane potentials between -40 and +80 mV (37 degrees C). Peak Ca2+ transients increased by two-fold in OVX myocytes when compared to sham, and Ca2+ transient rates of rise and decay were faster in OVX cells. In contrast, Ca2+ current densities were similar in sham and OVX cells. Sarcoplasmic reticulum (SR) Ca2+ content, assessed by caffeine, also was higher in OVX compared to sham cells (111.7 +/- 11.9 vs. 61.2 +/- 10.4 nM; p<0.05). Furthermore, the gain of Ca2+ release (Ca2+ release/Ca2+ current) was significantly greater in OVX than in sham cells (16.3 +/- 2.5 vs. 7.7 +/- 2.0 nM/pApF(-1) at 0 my; p<0.05). As changes in unitary Ca2+ release might account for the increased gain in OVX cells, spontaneous Ca2+ sparks were compared in fluo-4-loaded myocytes (37 degrees C). Spark frequency was higher in OVX cells than in sham cells. In addition, spark amplitudes were greater in OVX than in sham myocytes (Delta 6F/F-0=0.379 +/- 0.006 vs. 0342 +/- 0.006; p<0.05). However, spark widths and time courses were similar in the two groups. These data suggest that the size of individual SR Ca2+ release units is larger and the SR Ca2+ content is greater in myocytes of OVX mice, producing augmented gain and SR Ca2+ release. These observations show that OVX disrupts intracellular Ca2+ homeostasis and suggest that sex steroid hormones modulate unitary Ca2+ release in individual cardiac myocytes. (C) 2011 Elsevier Ltd. All rights reserved.