In order to understand the role of the dihydropyridine receptor in excitation-contraction coupling in cardiac cells, a thorough study of the structure and function of this molecule is warranted. During the purification of the dihydropyridine receptor on lectin-affinity columns and sucrose density gradients, a high molecular weight protein (360 kDa) was found to co-purify with the receptor. Since several high molecular weight proteins such as ion channels and dystrophin are associated with the cell membrane, the relationship of the 360 kDa protein to these proteins was investigated. The relationship of the 360 kDa protein with other high molecular weight proteins such as dystrophin was investigated using anti-peptide antibodies against dystrophin. The results suggested that the 360 kDa protein was related to $\alpha\sb2$-macroglobulin. In view of the function of $\alpha\sb2$-macroglobulin as a protease inhibitor, it is speculated that the 360 kDa protein may be performing a similar function in heart cells. The rise in Ca$\sp{2+}$ during systole may lead to activation of Ca$\sp{2+}$-sensitive proteases and the presence of a protease inhibitor in these cells may help prevent the proteolytic degradation of essential proteins such as ion channels and dystrophin. Increased proteolytic degradation in Duchenne muscular dystrophy has been shown to be due to high intracellular Ca$\sp{2+}$ levels as a result of sarcolemmal membrane damage. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/7676 |
| Date | January 1992 |
| Creators | Peri, Vita. |
| Contributors | Tuana, B. S., |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Detected Language | English |
| Type | Thesis |
| Format | 128 p. |
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