A carboxyl terminal peptide of the [alpha]1 subunit of the
dihydropyridine receptor inhibits calcium release channels.
Slavik, Kenneth J., Jian-Ping Wang, Bahman Aghdasi, Jia-Zheng Zhang,
and Frederic Mandel, Nadia Malouf and Susan L. Hamilton.
Department of Molecular Physiology and Biophysics, Baylor College
of Medicine, Houston, Texas 77030, Department of Biology, University
of North Carolina at Chapel Hill, North Carolina
APStracts 3:0369C, 1996.
Excitation-contraction coupling in skeletal muscle is thought to
involve a physical interaction between the [alpha]1 subunit of the
dihydropyridine receptor (DHPR) and the sarcoplasmic reticulum
Ca2& release channel (also known as the ryanodine receptor,
RyR1). Considerable evidence has accumulated to suggest that the
cytoplasmic loop between domains II and III of the DHPR [alpha]1
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 carboxyl terminus of the
[alpha]1 subunit inhibits both [3H]ryanodine binding to skeletal and
cardiac sarcoplasmic reticulum membranes and the activity of skeletal
SR calcium 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 E.coli and corresponding to amino
acids 1381 to 1627 and encompassing the above sequence has similar
effects. This portion of the [alpha]1 subunit of the t-tubule
dihydropyridine receptor is, therefore, a candidate for contributing
to the interaction of this protein with the Ca2& release channel.
Received 23 August 1996; accepted in final form 11 November 1996.
APS Manuscript Number C495-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996