Effects of Potassium Channel Toxins from Leiurus Quinquestriatus Hebraeus Venom on Responses to Cromakalim in Rabbit Blood Vessels

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1989 Nov 1

PMID 2531622

Citations 7

Authors

P N Strong

S W Weir

D J Beech

P Hiestand

H P Kocher

Affiliations

Soon will be listed here.

Abstract

1. The effects of fractionated Leiurus quinquestriatus hebraeus venom on cromakalim-induced 86Rb+ efflux in rabbit aortic smooth muscle were examined. 2. Crude venom (0.1-30 micrograms ml-1) produced a concentration-dependent decrease of 1 microM cromakalim-induced 86Rb+ response. The maximum blocking activity attainable was approximately 60%. 3. Fractionation of crude venom by gel permeation chromatography and subsequent chromatography on a cation ion-exchange column, produced two fractions (X and XI), active in the 86Rb+ blocking assay. 4. Fraction XII contained charybdotoxin (approximately 85% pure). After a final high performance liquid chromatography (h.p.l.c.) purification step, the purified toxin failed to inhibit the cromakalim-stimulated 86Rb+ efflux although it was a potent inhibitor of A23187-induced K+ flux in human erythrocytes and the large conductance calcium-activated potassium channel in rabbit portal vein smooth muscle. 5. Subsequent purification of fraction X by h.p.l.c. yielded a minor peak which contained 86Rb+ blocking activity. This subfraction was also capable of inhibiting apamin-sensitive, angiotensin II-stimulated K+ flux in guinea-pig hepatocytes. 6. It is concluded that the potassium channel opened by cromakalim in rabbit aortic smooth muscle is not blocked by charybdotoxin but by another distinct toxin in the venom of Leiurus quinquestriatus hebraeus.

Citing Articles

Characterization of Ca(2+)-activated 86Rb+ fluxes in rat C6 glioma cells: a system for identifying novel IKCa-channel toxins.

Bolsover S, Nowicky A, Strong P Br J Pharmacol. 1996; 117(3):479-487.

PMID: 8821537 PMC: 1909309. DOI: 10.1111/j.1476-5381.1996.tb15215.x.

High-conductance calcium-activated potassium channels; structure, pharmacology, and function.

Kaczorowski G, Knaus H, Leonard R, McManus O, Garcia M J Bioenerg Biomembr. 1996; 28(3):255-67.

PMID: 8807400 DOI: 10.1007/BF02110699.

Single channel and whole-cell K-currents evoked by levcromakalim in smooth muscle cells from the rabbit portal vein.

Beech D, Zhang H, Nakao K, Bolton T Br J Pharmacol. 1993; 110(2):583-90.

PMID: 8242233 PMC: 2175920. DOI: 10.1111/j.1476-5381.1993.tb13850.x.

Use of toxins to study potassium channels.

Garcia M, Galvez A, Garcia-Calvo M, King V, Vazquez J, Kaczorowski G J Bioenerg Biomembr. 1991; 23(4):615-46.

PMID: 1917911 DOI: 10.1007/BF00785814.

Characterization of potassium currents modulated by BRL 38227 in rat portal vein.

Noack T, Deitmer P, Edwards G, Weston A Br J Pharmacol. 1992; 106(3):717-26.

PMID: 1504756 PMC: 1907537. DOI: 10.1111/j.1476-5381.1992.tb14400.x.

References

Abia A, Lobaton C, Moreno A, Garcia-Sancho J . Leiurus quinquestriatus venom inhibits different kinds of Ca2+-dependent K+ channels. Biochim Biophys Acta. 1986; 856(2):403-7. DOI: 10.1016/0005-2736(86)90054-4. View

Inoue R, Kitamura K, Kuriyama H . Two Ca-dependent K-channels classified by the application of tetraethylammonium distribute to smooth muscle membranes of the rabbit portal vein. Pflugers Arch. 1985; 405(3):173-9. DOI: 10.1007/BF00582557. View

Smith C, Phillips M, Miller C . Purification of charybdotoxin, a specific inhibitor of the high-conductance Ca2+-activated K+ channel. J Biol Chem. 1986; 261(31):14607-13. View

Castle N, Strong P . Identification of two toxins from scorpion (Leiurus quinquestriatus) venom which block distinct classes of calcium-activated potassium channel. FEBS Lett. 1986; 209(1):117-21. DOI: 10.1016/0014-5793(86)81095-x. View

Guggino S, Guggino W, Green N, SACKTOR B . Blocking agents of Ca2+-activated K+ channels in cultured medullary thick ascending limb cells. Am J Physiol. 1987; 252(2 Pt 1):C128-37. DOI: 10.1152/ajpcell.1987.252.2.C128. View

Quast U . Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein. Br J Pharmacol. 1987; 91(3):569-78. PMC: 1853539. DOI: 10.1111/j.1476-5381.1987.tb11250.x. View

Papazian D, Schwarz T, Tempel B, Jan Y, Jan L . Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. Science. 1987; 237(4816):749-53. DOI: 10.1126/science.2441470. View

Hermann A, Erxleben C . Charybdotoxin selectively blocks small Ca-activated K channels in Aplysia neurons. J Gen Physiol. 1987; 90(1):27-47. PMC: 2228863. DOI: 10.1085/jgp.90.1.27. View

Benham C, Bolton T . Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of the rabbit. J Physiol. 1986; 381:385-406. PMC: 1182985. DOI: 10.1113/jphysiol.1986.sp016333. View

10.

Valdivia H, Smith J, Martin B, Coronado R, Possani L . Charybdotoxin and noxiustoxin, two homologous peptide inhibitors of the K+ (Ca2+) channel. FEBS Lett. 1988; 226(2):280-4. DOI: 10.1016/0014-5793(88)81439-x. View

11.

Quast U, Cook N . Leiurus quinquestriatus venom inhibits BRL 34915-induced 86Rb+ efflux from the rat portal vein. Life Sci. 1988; 42(7):805-10. DOI: 10.1016/0024-3205(88)90654-6. View

12.

Lewis R, Cahalan M . Subset-specific expression of potassium channels in developing murine T lymphocytes. Science. 1988; 239(4841 Pt 1):771-5. DOI: 10.1126/science.2448877. View

13.

Cook N, Quast U, Hof R, Baumlin Y, Pally C . Similarities in the mechanism of action of two new vasodilator drugs: pinacidil and BRL 34915. J Cardiovasc Pharmacol. 1988; 11(1):90-9. DOI: 10.1097/00005344-198801000-00014. View

14.

Tempel B, Jan Y, Jan L . Cloning of a probable potassium channel gene from mouse brain. Nature. 1988; 332(6167):837-9. DOI: 10.1038/332837a0. View

15.

Gimenez-Gallego G, Navia M, Reuben J, KATZ G, Kaczorowski G, Garcia M . Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of calcium-activated potassium channels. Proc Natl Acad Sci U S A. 1988; 85(10):3329-33. PMC: 280202. DOI: 10.1073/pnas.85.10.3329. View

16.

Chicchi G, Gimenez-Gallego G, Ber E, Garcia M, Winquist R, Cascieri M . Purification and characterization of a unique, potent inhibitor of apamin binding from Leiurus quinquestriatus hebraeus venom. J Biol Chem. 1988; 263(21):10192-7. View

17.

Pongs O, Kecskemethy N, Muller R, Krah-Jentgens I, Baumann A, Kiltz H . Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. EMBO J. 1988; 7(4):1087-96. PMC: 454441. DOI: 10.1002/j.1460-2075.1988.tb02917.x. View

18.

Baumann A, Grupe A, Ackermann A, Pongs O . Structure of the voltage-dependent potassium channel is highly conserved from Drosophila to vertebrate central nervous systems. EMBO J. 1988; 7(8):2457-63. PMC: 457115. DOI: 10.1002/j.1460-2075.1988.tb03092.x. View

19.

Cook N, Weir S, Danzeisen M . Anti-vasoconstrictor effects of the K+ channel opener cromakalim on the rabbit aorta--comparison with the calcium antagonist isradipine. Br J Pharmacol. 1988; 95(3):741-52. PMC: 1854243. DOI: 10.1111/j.1476-5381.1988.tb11700.x. View

20.

Cook N . The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci. 1988; 9(1):21-8. DOI: 10.1016/0165-6147(88)90238-6. View