Diversity of atrial local Ca2+ signalling: evidence from 2-D confocal imaging in Ca2+-buffered rat atrial myocytes.
Diversity of atrial local Ca2+ signalling: evidence from 2-D confocal imaging in Ca2+-buffered rat atrial myocytes.
复制标题
心房局部 Ca2 信号传导的多样性：来自 Ca2 缓冲大鼠心房肌细胞的二维共聚焦成像的证据。
DOI：
10.1113/jphysiol.2005.092270
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Morad,Martin
中科院分区：
文献类型：
--
作者：
Woo,Sun-Hee;Cleemann,Lars;Morad,Martin
Atrial myocytes, lacking t‐tubules, have two functionally separate groups of ryanodine receptors (RyRs): those at the periphery colocalized with dihydropyridine receptors (DHPRs), and those at the cell interior not associated with DHPRs. We have previously shown that the Ca2+current (ICa)‐gated central Ca2+release has a fast component that is followed by a slower and delayed rising phase. The mechanisms that regulate the central Ca2+releases remain poorly understood. The fast central release component is highly resistant to dialysed Ca2+buffers, while the slower, delayed component is completely suppressed by such exogenous buffers. Here we used dialysis of Ca2+buffers (EGTA) into voltage‐clamped rat atrial myocytes to isolate the fast component of central Ca2+release and examine its properties using rapid (240 Hz) two‐dimensional confocal Ca2+imaging. We found two populations of rat atrial myocytes with respect to the ratio of central to peripheral Ca2+release (Rc/p). In one population (‘group 1’, ∼60% of cells),Rc/pconverged on 0.2, while in another population (‘group 2’, ∼40%),Rc/phad a Gaussian distribution with a mean value of 0.625. The fast central release component of group 2 cells appeared to result from in‐focus Ca2+sparks on activation ofICa. In group 1 cells intracellular membranes associated with t‐tubular structures were never seen using short exposures to membrane dyes. In most of the group 2 cells, a faint intracellular membrane staining was observed. Quantification of caffeine‐releasable Ca2+pools consistently showed larger central Ca2+stores in group 2 and larger peripheral stores in group 1 cells. TheRc/pwas larger at more positive and negative voltages in group 1 cells. In contrast, in group 2 cells, theRc/pwas constant at all voltages. In group 1 cells the gain of peripheral Ca2+release sites (Δ[Ca2+]/ICa) was larger at −30 than at +20 mV, but significantly dampened at the central sites. On the other hand, the gains of peripheral and central Ca2+releases in group 2 cells showed no voltage dependence. Surprisingly, the voltage dependence of the fast central release component was bell‐shaped and similar to that ofICain both cell groups. Removal of extracellular Ca2+or application of Ni2+(5 mm) suppressed equallyICaand Ca2+release from the central release sites at +60 mV. Depolarization to +100 mV, whereICais absent and the Na+–Ca2+exchanger (NCX) acts in reverse mode, did not trigger the fast central Ca2+releases in either group, but brief reduction of [Na+]oto levels equivalent to [Na+]ifacilitated fast peripheral and central Ca2+releases in group 2 myocytes, but not in group 1 myocytes. In group 2 cells, long‐lasting (> 1 min) exposures to caffeine (10 mm) or ryanodine (20 μm) significantly suppressedICa‐triggered central and peripheral Ca2+releases. Our data suggest significant diversity of local Ca2+signalling in rat atrial myocytes. In one group,ICa‐triggered peripheral Ca2+release propagates into the interior triggering central Ca2+release with significant delay. In a second group of myocytesICatriggers a significant number of central sites as rapidly and effectively as the peripheral sites, thereby producing more synchronized Ca2+releases throughout the myocytes. The possible presence of vestigial t‐tubules and larger Ca2+content of central sarcoplasmic reticulum (SR) in group 2 cells may be responsible for the rapid and strong activation of central release of Ca2+in this subset of atrial myocytes.
