Pharmaceuticals 2010, 3(4), 1093-1107; doi:10.3390/ph3041093
Article

Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+-Release Channels/Ryanodine Receptors

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Received: 18 March 2010; Accepted: 11 April 2010 / Published: 13 April 2010
(This article belongs to the Special Issue Cell-penetrating Peptides)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Scorpion venoms are rich in ion channel-modifying peptides, which have proven to be invaluable probes of ion channel structure-function relationship. We previously isolated imperatoxin A (IpTxa), a 3.7 kDa peptide activator of Ca2+-release channels/ryanodine receptors (RyRs) [1,2,3] and founding member of the calcin family of scorpion peptides. IpTxa folds into a compact, mostly hydrophobic molecule with a cluster of positively-charged, basic residues polarized on one side of the molecule that possibly interacts with the phospholipids of cell membranes. To investigate whether IpTxa permeates external cellular membranes and targets RyRs in vivo, we perfused IpTxa on intact cardiomyocytes while recording field-stimulated intracellular Ca2+ transients. To further investigate the cell-penetrating capabilities of the toxin, we prepared thiolated, fluorescent derivatives of IpTxa. Biological activity and spectroscopic properties indicate that these derivatives retain high affinity for RyRs and are only 5- to 10-fold less active than native IpTxa. Our results demonstrate that IpTxa is capable of crossing cell membranes to alter the release of Ca2+ in vivo, and has the capacity to carry a large, membrane-impermeable cargo across the plasma membrane, a finding with exciting implications for novel drug delivery.
Keywords: imperatoxin; ryanodine receptors; cell-penetrating peptide; calcin; drug delivery
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MDPI and ACS Style

Gurrola, G.B.; Capes, E.M.; Zamudio, F.Z.; Possani, L.D.; Valdivia, H.H. Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+-Release Channels/Ryanodine Receptors. Pharmaceuticals 2010, 3, 1093-1107.

AMA Style

Gurrola GB, Capes EM, Zamudio FZ, Possani LD, Valdivia HH. Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+-Release Channels/Ryanodine Receptors. Pharmaceuticals. 2010; 3(4):1093-1107.

Chicago/Turabian Style

Gurrola, Georgina B.; Capes, E. Michelle; Zamudio, Fernando Z.; Possani, Lourival D.; Valdivia, Héctor H. 2010. "Imperatoxin A, a Cell-Penetrating Peptide from Scorpion Venom, as a Probe of Ca2+-Release Channels/Ryanodine Receptors." Pharmaceuticals 3, no. 4: 1093-1107.

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