AJP - Cell Physiology, Vol 269, Issue 1 C1-10, Copyright © 1995 by American Physiological Society

ARTICLES

Charybdotoxin and its effects on potassium channels

M. L. Garcia, H. G. Knaus, P. Munujos, R. S. Slaughter and G. J. Kaczorowski
Department of Membrane Biochemistry and Biophysics, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

Over the last few years, a considerable amount of information has been obtained regarding K+ channels. Different areas of research have contributed to knowledge in this field. Charybdotoxin (ChTX), a 37-amino acid peptide isolated from venom of the scorpion Leiurus quinquestriatus var. hebraeus, represents a remarkable tool for studying K+ channels. With its use, it has been possible to purify the high-conductance Ca(2+)-activated K+ (maxi-K) channel to homogeneity and determine the subunit composition of this channel. This has led to the discovery of an auxiliary beta-subunit that, when coexpressed with the pore-forming subunit, mSlo, alters the biophysical and pharmacological properties of this latter subunit. With the feasibility of producing large amounts of ChTX by recombinant techniques and the knowledge of the three-dimensional structure of the peptide, it has been possible to carry out site-directed mutagenesis studies and obtain a picture of the interaction surface of the toxin with two channels, maxi-K and Shaker, and to derive a picture of the complementary surface of the receptor in these two channels. Finally, ChTX, and the more selective K+ channel toxins that were subsequently discovered, have provided us with unique tools not only to determine the functional role that K+ channels play in target tissues but also to develop the molecular pharmacology of these channels.

This article has been cited by other articles:

				A. Mobasheri, T. C. Gent, M. D. Womack, S. D. Carter, P. D. Clegg, and R. Barrett-Jolley Quantitative analysis of voltage-gated potassium currents from primary equine (Equus caballus) and elephant (Loxodonta africana) articular chondrocytes Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R172 - R180. [Abstract] [Full Text] [PDF]

				Y. Yashiro and B. R. Duling Participation of intracellular Ca2+ stores in arteriolar conducted responses Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H65 - H73. [Abstract] [Full Text] [PDF]

				C.-X. Fan, X.-K. Chen, C. Zhang, L.-X. Wang, K.-L. Duan, L.-L. He, Y. Cao, S.-Y. Liu, M.-N. Zhong, C. Ulens, et al. A Novel Conotoxin from Conus betulinus, kappa -BtX, Unique in Cysteine Pattern and in Function as a Specific BK Channel Modulator J. Biol. Chem., April 4, 2003; 278(15): 12624 - 12633. [Abstract] [Full Text] [PDF]

				L. Offertaler, F.-M. Mo, S. Batkai, J. Liu, M. Begg, R. K. Razdan, B. R. Martin, R. D. Bukoski, and G. Kunos Selective Ligands and Cellular Effectors of a G Protein-Coupled Endothelial Cannabinoid Receptor Mol. Pharmacol., March 1, 2003; 63(3): 699 - 705. [Abstract] [Full Text] [PDF]

				B. Hoepfl, B. Rodenwaldt, U. Pohl, and C. de Wit EDHF, but not NO or prostaglandins, is critical to evoke a conducted dilation upon ACh in hamster arterioles Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H996 - H1004. [Abstract] [Full Text] [PDF]

				P. Coats, F. Johnston, J. MacDonald, J. J. V. McMurray, and C. Hillier Endothelium-Derived Hyperpolarizing Factor : Identification and Mechanisms of Action in Human Subcutaneous Resistance Arteries Circulation, March 27, 2001; 103(12): 1702 - 1708. [Abstract] [Full Text] [PDF]

				N. Paolocci, P. Pagliaro, T. Isoda, F. W. Saavedra, and D. A. Kass Role of Calcium-Sensitive K+ Channels and Nitric Oxide in In Vivo Coronary Vasodilation From Enhanced Perfusion Pulsatility Circulation, January 2, 2001; 103(1): 119 - 124. [Abstract] [Full Text] [PDF]

				H. Rauer, M. D. Lanigan, M. W. Pennington, J. Aiyar, S. Ghanshani, M. D. Cahalan, R. S. Norton, and K. G. Chandy Structure-guided Transformation of Charybdotoxin Yields an Analog That Selectively Targets Ca2+-activated over Voltage-gated K+ Channels J. Biol. Chem., January 14, 2000; 275(2): 1201 - 1208. [Abstract] [Full Text] [PDF]

				M. Grunnet, H.-G. Knaus, C. Solander, and D. A. Klaerke Quantification and distribution of Ca2+-activated maxi K+ channels in rabbit distal colon Am J Physiol Gastrointest Liver Physiol, July 1, 1999; 277(1): G22 - G30. [Abstract] [Full Text] [PDF]

				K. Turnheim, J. Gruber, C. Wachter, and V. Ruiz-Gutierrez Membrane phospholipid composition affects function of potassium channels from rabbit colon epithelium Am J Physiol Cell Physiol, July 1, 1999; 277(1): C83 - C90. [Abstract] [Full Text] [PDF]

				A. Abderrahmane, D. Salvail, M. Dumoulin, J. Garon, A. Cadieux, and E. Rousseau Direct Activation of KCa Channel in Airway Smooth Muscle by Nitric Oxide: Involvement of a Nitrothiosylation Mechanism? Am. J. Respir. Cell Mol. Biol., September 1, 1998; 19(3): 485 - 497. [Abstract] [Full Text]

				J. R. López-López, M. T. Pérez-García, E. Canet, and C. Gonzalez Effects of Almitrine Bismesylate on the Ionic Currents of Chemoreceptor Cells from the Carotid Body Mol. Pharmacol., February 1, 1998; 53(2): 330 - 339. [Abstract] [Full Text]

				S. L. Archer, J. M.C. Huang, H. L. Reeve, V. Hampl, S. Tolarova, E. Michelakis, and E. K. Weir Differential Distribution of Electrophysiologically Distinct Myocytes in Conduit and Resistance Arteries Determines Their Response to Nitric Oxide and Hypoxia Circ. Res., March 1, 1996; 78(3): 431 - 442. [Abstract] [Full Text]