Sex differences in mechanisms of cardiac excitation-contraction coupling in rat ventricular myocytes
Sex differences in mechanisms of cardiac excitation-contraction coupling in rat ventricular myocytes
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DOI：
10.1152/ajpheart.00299.2010
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发表时间：
2010-07-01
影响因子：
4.8
通讯作者：
Howlett, Susan E.
中科院分区：
文献类型：
--
作者：
Farrell, Spring R.;Ross, Jenna L.;Howlett, Susan E.
法雷尔·SR，罗斯·J·L，豪利特·SE。大鼠心肌细胞兴奋收缩偶联机制的性别差异。Am J Physiol心脏圈Physiol 299：H36-H45,2010。2010年5月7日首次出版；DOI：10.1152/ajpheart.00299.2010。-比较了3个月龄雄性和雌性大鼠分离的心室肌细胞兴奋-收缩(E-C)偶联的成分。同时测量钙离子浓度(Fura-2)和细胞缩短(边缘检测器)(37℃)。用微电极测量膜电位和离子电流。雄性和雌性心肌细胞的动作电位相似，但雌性心肌细胞的收缩较小和缓慢。在电压钳制细胞中，女性的收缩峰值小于男性(5.1+/-0.7%比7.7+/-0.8%，P<；0.05)。同样，女性的钙瞬变小于男性，女性的钙瞬变上升速度较慢。尽管女性的收缩和钙瞬变较小，但两组的钙电流密度相似。用咖啡因评估的肌浆网钙含量在性别之间没有差异。E-C偶联增益(钙释放/钙电流)女性小于男性(157.0+/-15.6vs.338.4+/-54.3nM/S/(pA/pF)，P<；0.05)。为了确定雌性细胞的增长减少是否是由于单一钙释放的变化，评估了自发的钙火花(Fluo-4，37℃)。两组的火花频率和宽度相似，但女性的火花幅度小于男性(0.56±-0.01比0.64+/-0.01 Delta F/F0，P<；0.05)。女性的火花持续时间也比男性短(半峰值全程=14.86+/-0.17vs.16.25+/-0.27ms，P<；0.05)。这些观察表明，钙火花的大小和持续时间的减少是女性心肌细胞E-C偶联增益降低的原因之一。因此，心脏收缩功能的差异在一定程度上是由于性别之间单一钙释放的差异。
Farrell SR, Ross JL, Howlett SE. Sex differences in mechanisms of cardiac excitation-contraction coupling in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 299: H36-H45, 2010. First published May 7, 2010; doi:10.1152/ajpheart.00299.2010.-Components of excitation-contraction (E-C) coupling were compared in ventricular myocytes isolated from 3-mo-old male and female rats. Ca2+ concentrations (fura-2) and cell shortening (edge detector) were measured simultaneously (37 degrees C). Membrane potential and ionic currents were measured with microelectrodes. Action potentials were similar in male and female myocytes, but contractions were smaller and slower in females. In voltage-clamped cells, peak contractions were smaller in females than in males (5.1 +/- 0.7% vs. 7.7 +/- 0.8% diastolic length, P < 0.05). Similarly, Ca2+ transients were smaller in females than in males and the rate of rise of the Ca2+ transient was slower in females. Despite smaller contractions and Ca2+ transients in females, Ca2+ current density was similar in both groups. Sarcoplasmic reticulum Ca2+ content, assessed with caffeine, did not differ between the sexes. However, E-C coupling gain (rate of Ca2+ release/Ca2+ current) was smaller in females than in males (157.0 +/- 15.6 vs. 338.4 +/- 54.3 (nM/s)/(pA/pF), P < 0.05). To determine whether the reduced gain in female cells was due to changes in unitary Ca2+ release, spontaneous Ca2+ sparks were evaluated (fluo-4, 37 degrees C). Spark frequencies and widths were similar in both groups, but spark amplitudes were smaller in females than in males (0.56 +/- 0.01 vs. 0.64 +/- 0.01 Delta F/F0, P < 0.05). Spark durations also were shorter in females than in males (full duration at half-maximum = 14.86 +/- 0.17 vs. 16.25 +/- 0.27 ms, P < 0.05). These observations suggest that decreases in the size and duration of Ca2+ sparks contributes to the decrease in E-C coupling gain in female myocytes. Thus, differences in cardiac contractile function arise, in part, from differences in unitary Ca2+ release between the sexes.