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This Article Full Text Full Text (PDF) All Versions of this Article: 567/3/905    most recent jphysiol.2005.092270v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woo, S.-H. Articles by Morad, M. Search for Related Content PubMed PubMed Citation Articles by Woo, S.-H. Articles by Morad, M.

¹ Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA
² College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea

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 (I_Ca)-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 (R_c/p). In one population (‘group 1’, 60% of cells), R_c/p converged on 0.2, while in another population (‘group 2’, 40%), R_c/p had 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 of I_Ca. 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. The R_c/p was larger at more positive and negative voltages in group 1 cells. In contrast, in group 2 cells, the R_c/p was constant at all voltages. In group 1 cells the gain of peripheral Ca²⁺ release sites ([Ca²⁺]/I_Ca) 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 of I_Ca in both cell groups. Removal of extracellular Ca²⁺ or application of Ni²⁺ (5 mM) suppressed equally I_Ca and Ca²⁺ release from the central release sites at +60 mV. Depolarization to +100 mV, where I_Ca is 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⁺]_o to levels equivalent to [Na⁺]_i facilitated 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 suppressed I_Ca-triggered central and peripheral Ca²⁺ releases. Our data suggest significant diversity of local Ca²⁺ signalling in rat atrial myocytes. In one group, I_Ca-triggered peripheral Ca²⁺ release propagates into the interior triggering central Ca²⁺ release with significant delay. In a second group of myocytes I_Ca triggers 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.

(Received 8 June 2005; accepted after revision 13 July 2005; first published online 14 July 2005)
Corresponding author M. Morad: Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA. Email: moradm{at}georgetown.edu

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