A carboxy-terminal peptide of the α1-subunit of the dihydropyridine receptor inhibits Ca2+-release channels

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Excitation-contraction coupling in skeletal muscle is thought to involve a physical interaction between the α1-subunit of the dihydropyridine receptor (DHPR) and the sarcoplasmic reticulum (SR) Ca2+-release channel (also known as the ryanodine receptor). Considerable evidence has accumulated to suggest that the cytoplasmic loop between domains II and III of the DHPR α1-subunit is at least partially responsible for this interaction. Other parts of this subunit or other subunits may, however, contribute to the functional and/or structural coupling between these two proteins. A synthetic peptide corresponding to a conserved sequence located between amino acids 1487 and 1506 in the carboxy terminus of the α1-subunit inhibits both [3H]ryanodine binding to skeletal and cardiac SR membranes and the activity of skeletal SR Ca2+-release channels reconstituted into planar lipid bilayers. A second, multiantigenic peptide synthesized to correspond to the same sequence inhibits both binding and channel activity at lower concentrations than the linear peptide. These peptides slow the rate at which [3H]ryanodine binds to its high-affinity binding site and decrease the rate at which [3H]ryanodine dissociates from this site. A third polypeptide synthesized in Escherichia coli and corresponding to amino acids 1381-1627 and encompassing the above sequence has similar effects. This portion of the α1-subunit of the transverse tubule DHPR is therefore a candidate for contributing to the interaction of this protein with the Ca2+-release channel.

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American Journal of Physiology - Cell Physiology




5 41-5

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This article was published in American Journal of Physiology - Cell Physiology, Volume 272, Issue 5 41-5, Pages C1475-C1481.

The published version is available at http://ajpcell.physiology.org/ .

Copyright © 1997.

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