Skeletal and Cardiac Ryanodine Receptors Exhibit Different Responses to Ca2+ Overload and Luminal Ca2+
| Autor: | Huihui Kong, Y. Shimoni, Henry J. Duff, Lin Zhang, S.R. Wayne Chen, Ruiwu Wang, Keyun Chen, Wenqian Chen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Muscle Fibers Skeletal Biophysics Biology Kidney Ryanodine receptor 2 Cell Line 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Myocyte Myocytes Cardiac Calcium Signaling Channels Receptors and Electrical Signaling 030304 developmental biology Calcium signaling RYR1 0303 health sciences Ryanodine receptor Endoplasmic reticulum Skeletal muscle Kidney metabolism Ryanodine Receptor Calcium Release Channel musculoskeletal system Cell biology Endocrinology medicine.anatomical_structure cardiovascular system Calcium tissues 030217 neurology & neurosurgery |
| Zdroj: | Biophysical Journal. 92(8):2757-2770 |
| ISSN: | 0006-3495 |
| DOI: | 10.1529/biophysj.106.100545 |
| Popis: | Spontaneous Ca(2+) release occurs in cardiac cells during sarcoplasmic reticulum Ca(2+) overload, a process we refer to as store-overload-induced Ca(2+) release (SOICR). Unlike cardiac cells, skeletal muscle cells exhibit little SOICR activity. The molecular basis of this difference is not well defined. In this study, we investigated the SOICR properties of HEK293 cells expressing RyR1 or RyR2. We found that HEK293 cells expressing RyR2 exhibited robust SOICR activity, whereas no SOICR activity was observed in HEK293 cells expressing RyR1. However, in the presence of low concentrations of caffeine, SOICR could be triggered in these RyR1-expressing cells. At the single-channel level, we showed that RyR2 is much more sensitive to luminal Ca(2+) than RyR1. To identify the molecular determinants responsible for these differences, we constructed two chimeras between RyR1 and RyR2, N-RyR1(1-4006)/C-RyR2(3962-4968) and N-RyR2(1-3961)/C-RyR1(4007-5037). We found that replacing the C-terminal region of RyR1 with the corresponding region of RyR2 (N-RyR1/C-RyR2) dramatically enhanced the propensity for SOICR and the response to luminal Ca(2+), whereas replacing the C-terminal region of RyR2 with the corresponding region of RyR1 (N-RyR2/C-RyR1) reduced the propensity for SOICR and the luminal Ca(2+) response. These observations indicate that the C-terminal region of RyR is a critical determinant of both SOICR and the response to luminal Ca(2+). These chimeric studies also reveal that the N-terminal region of RyR plays an important role in regulating SOICR and luminal Ca(2+) response. Taken together, our results demonstrate that RyR1 differs markedly from RyR2 with respect to their responses to Ca(2+) overload and luminal Ca(2+), and suggest that the lack of spontaneous Ca(2+) release in skeletal muscle cells is, in part, attributable to the unique intrinsic properties of RyR1. |
| Databáze: | OpenAIRE |
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