Woo Sun-Hee, Cleemann Lars, Morad Martin
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA.
Circ Res. 2003 Jan 10;92(1):e1-11. doi: 10.1161/01.res.0000051887.97625.07.
Atrial myocytes have two functionally separate Ca2+ release sites: those in peripheral sarcoplasmic reticulum (SR) adjacent to the Ca2+ channels of surface membrane and those in central SR not associated with Ca2+ channels. Recently, we have reported on the gating of these two different Ca2+ release sites by Ca2+ current. In the present study, we report on the spatiotemporal properties of focal Ca2+ releases (sparks) occurring spontaneously in central and peripheral sites of voltage-clamped rat atrial myocytes, using rapid 2-dimensional (2-D) confocal Ca2+ imaging. Peripheral and central sparks were similar in size and release time (approximately 300 000 Ca2+ ions for congruent with 12 ms), but significantly larger and longer than ventricular sparks. Both sites were resistant to Cd2+ and inhibited by ryanodine. Peripheral sparks were brighter and flattened against surface membrane, had approximately 5-fold higher frequency, approximately 2 times faster diffusion coefficient, and dissipated abruptly. Central sparks, in contrast, occurred less frequently, were elongated along the cellular longitudinal axis, and dissipated slowly. Compound sparks (composed of 2 to 5 unitary focal releases) aligned longitudinally and occurred more frequently at the center. The diversity of peripheral and central sparks with respect to shape, frequency, and speed of spatial development and decay is consistent with regional ultrastructural heterogeneity of SR. The retarded dissipation of central atrial sparks, and high prevalence of compound sparks in cell center may be critical in facilitating the propagation of Ca2+ waves in atrial myocytes lacking t-tubular system and provide the atrial myocytes with functional Ca2+ signaling diversity. The full text of this article is available at http://www.circresaha.org.
心房肌细胞有两个功能上相互独立的Ca2+释放位点:一个位于与表面膜Ca2+通道相邻的外周肌浆网(SR)中,另一个位于与Ca2+通道无关的中央SR中。最近,我们报道了这两个不同Ca2+释放位点受Ca2+电流的门控情况。在本研究中,我们利用快速二维(2-D)共聚焦Ca2+成像技术,报道了电压钳制的大鼠心房肌细胞中央和外周位点自发发生的局灶性Ca2+释放(钙火花)的时空特性。外周和中央钙火花在大小和释放时间上相似(约300 000个Ca2+离子,持续12毫秒),但比心室钙火花明显更大、持续时间更长。两个位点均对Cd2+有抗性,并受ryanodine抑制。外周钙火花更亮,紧贴表面膜变平,频率约高5倍,扩散系数约快2倍,且突然消散。相比之下,中央钙火花出现频率较低,沿细胞纵轴拉长,消散缓慢。复合钙火花(由2至5个单一局灶性释放组成)沿纵向排列,在细胞中央出现频率更高。外周和中央钙火花在形状、频率以及空间发展和衰减速度方面的差异与SR的区域超微结构异质性一致。中央心房钙火花消散延迟以及复合钙火花在细胞中央的高发生率可能对促进缺乏T小管系统的心房肌细胞中Ca2+波的传播至关重要,并为心房肌细胞提供功能性Ca2+信号多样性。本文全文可在http://www.circresaha.org获取。