Calciseptine, a Ca2+ Channel Blocker, Has Agonist Actions on L-type Ca2+ Currents of Frog and Mammalian Skeletal Muscle

Calciseptine, a Ca2+ Channel Blocker, Has Agonist Actions on L-type Ca2+ Currents of Frog and... Calciseptine is a natural peptide consisting of 60 amino acids with four disulfide bonds. The peptide is a natural L-type Ca2+-channel blocker in heart and other systems, but its actions in skeletal muscle have not been previously described. The aim of this study is to characterize the effects of calciseptine on L-type Ca2+ channels of skeletal muscle and on contraction. Whole-cell, patch-clamp experiments were performed to record Ca2+ currents (I Ca) from mouse myotubes, whereas Vaseline-gap voltage-clamp experiments were carried out to record I Ca from frog skeletal muscle fibers. We found that calciseptine acts as a channel agonist in skeletal muscle, increasing peak I Ca by 37% and 49% in these two preparations. Likewise, the peptide increased intramembrane charge movement, though it had little effect on contraction. The molecular analysis of the peptide indicated the presence of a local, electrostatic potential that resembles that of the 1,4-dihydropyridine agonist Bay K 8644. These observations suggest that calciseptine shares the properties of 1,4-dihydropyridine derivatives in modulating the permeation of divalent cations through L-type channels. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Calciseptine, a Ca2+ Channel Blocker, Has Agonist Actions on L-type Ca2+ Currents of Frog and Mammalian Skeletal Muscle

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Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 2001 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-001-0080-7
Publisher site
See Article on Publisher Site

Abstract

Calciseptine is a natural peptide consisting of 60 amino acids with four disulfide bonds. The peptide is a natural L-type Ca2+-channel blocker in heart and other systems, but its actions in skeletal muscle have not been previously described. The aim of this study is to characterize the effects of calciseptine on L-type Ca2+ channels of skeletal muscle and on contraction. Whole-cell, patch-clamp experiments were performed to record Ca2+ currents (I Ca) from mouse myotubes, whereas Vaseline-gap voltage-clamp experiments were carried out to record I Ca from frog skeletal muscle fibers. We found that calciseptine acts as a channel agonist in skeletal muscle, increasing peak I Ca by 37% and 49% in these two preparations. Likewise, the peptide increased intramembrane charge movement, though it had little effect on contraction. The molecular analysis of the peptide indicated the presence of a local, electrostatic potential that resembles that of the 1,4-dihydropyridine agonist Bay K 8644. These observations suggest that calciseptine shares the properties of 1,4-dihydropyridine derivatives in modulating the permeation of divalent cations through L-type channels.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Nov 15, 2001

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