Lakatta Edward G, Maltsev Victor A, Bogdanov Konstantin Y, Stern Michael D, Vinogradova Tatiana M
Gerontology Research Center, Baltimore, Md 21224, USA.
Circ Res. 2003 Feb 21;92(3):e45-50. doi: 10.1161/01.res.0000055920.64384.fb.
While a diversity of cell types and distribution within the sinoatrial node and cell-cell interactions add complexity to a complete elucidation of the heart's pacemaker function, it has become clear that cyclic variation of submembrane [Ca2+] and activation of the Na+-Ca2+ exchanger during diastolic depolarization (DD) act in concert with ion channels to confer on sinoatrial node cells (SANCs) their status of dominance with respect to pacemaker function. Studies using confocal microscopy indicate that subsarcolemmal Ca2+ release via ryanodine receptors occurs not only in response to the action potential (AP) upstroke, but also during the DD, and this is augmented by beta-adrenergic receptor (beta-AR) stimulation. Spontaneous APs simulated by mathematical SANC models beat at a faster rate when this subsarcolemmal Ca2+ waveform measured under beta-AR stimulation is introduced into the modeling scheme. Thus, in future investigation of pacemaker functioning in health, disease, and disease therapies the "bar ought to be raised" to embrace the impact of cyclic variation in submembrane [Ca2+] on pacemaker function. The full text of this article is available at http://www.circresaha.org.
虽然窦房结内多种细胞类型及其分布以及细胞间相互作用增加了全面阐明心脏起搏器功能的复杂性，但已明确的是，舒张期去极化（DD）期间膜下[Ca2+]的周期性变化以及钠钙交换体的激活与离子通道协同作用，赋予窦房结细胞（SANC）在起搏器功能方面的主导地位。使用共聚焦显微镜的研究表明，通过兰尼碱受体的肌膜下Ca2+释放不仅发生在动作电位（AP）上升期，也发生在DD期间，并且β-肾上腺素能受体（β-AR）刺激会增强这种释放。当将在β-AR刺激下测量的这种肌膜下Ca2+波形引入建模方案时，由数学SANC模型模拟的自发性AP以更快的速率搏动。因此，在未来对健康、疾病及疾病治疗中起搏器功能的研究中，应该“提高标准”以纳入膜下[Ca2+]的周期性变化对起搏器功能的影响。本文全文可在http://www.circresaha.org获取。
