Abstract
Although the voltage-sensitive Ca channel present in Paramecium has been subjected to detailed physiological and genetic analysis, no organic ligands have been described that block this channel with high affinity and that ultimately can be used to identify channel components. Based on a previous observation that the naphthalene sulfonamide calmodulin antagonist W-7 can block Paramecium Ca channels at high concentration, we have synthesized analogs of W-7 that block these channels at concentrations of less than 1 microM. The effectiveness of these compounds was tested both by a sensitive behavioral assay and on Ca channels that had been incorporated into planar lipid bilayers. Despite the fact that these compounds are effective Paramecium calmodulin antagonists, two independent lines of evidence suggest that W-7 and its analogs block the Ca channel by a mechanism that is independent of their action on calmodulin. In addition, the sensitivity to W-7 or dihydropyridines of Ca channels present in a number of eukaryotic phyla has been used to identify similarities in Ca channels from widely diverse organisms. It appears that the pharmacological specificity provides a means to group Ca channels.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adoutte A., Ramanathan R., Lewis R. M., Dute R. R., Ling K. Y., Kung C., Nelson D. L. Biochemical studies of the excitable membrane of Paramecium tetraurelia. III. Proteins of cilia and ciliary membranes. J Cell Biol. 1980 Mar;84(3):717–738. doi: 10.1083/jcb.84.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Agnew W. S., Levinson S. R., Brabson J. S., Raftery M. A. Purification of the tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from Electrophorus electricus electroplax membranes. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2606–2610. doi: 10.1073/pnas.75.6.2606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armstrong C. M., Matteson D. R. Two distinct populations of calcium channels in a clonal line of pituitary cells. Science. 1985 Jan 4;227(4682):65–67. doi: 10.1126/science.2578071. [DOI] [PubMed] [Google Scholar]
- Carbone E., Lux H. D. A low voltage-activated calcium conductance in embryonic chick sensory neurons. Biophys J. 1984 Sep;46(3):413–418. doi: 10.1016/S0006-3495(84)84037-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coronado R., Latorre R. Phospholipid bilayers made from monolayers on patch-clamp pipettes. Biophys J. 1983 Aug;43(2):231–236. doi: 10.1016/S0006-3495(83)84343-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunham P., Anderson C., Rich A. M., Weissmann G. Stimulus-response coupling in sponge cell aggregation: Evidence for calcium as an intracellular messenger. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4756–4760. doi: 10.1073/pnas.80.15.4756. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dunlap K. Localization of calcium channels in Paramecium caudatum. J Physiol. 1977 Sep;271(1):119–133. doi: 10.1113/jphysiol.1977.sp011993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ehrlich B. E., Finkelstein A., Forte M., Kung C. Voltage-dependent calcium channels from Paramecium cilia incorporated into planar lipid bilayers. Science. 1984 Jul 27;225(4660):427–428. doi: 10.1126/science.6330895. [DOI] [PubMed] [Google Scholar]
- Ehrlich B. E., Schen C. R., Spudich J. L. Bacterial rhodopsins monitored with fluorescent dyes in vesicles and in vivo. J Membr Biol. 1984;82(1):89–94. doi: 10.1007/BF01870735. [DOI] [PubMed] [Google Scholar]
- Fedulova S. A., Kostyuk P. G., Veselovsky N. S. Two types of calcium channels in the somatic membrane of new-born rat dorsal root ganglion neurones. J Physiol. 1985 Feb;359:431–446. doi: 10.1113/jphysiol.1985.sp015594. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gietzen K., Wüthrich A., Bader H. R 24571: a new powerful inhibitor of red blood cell Ca++-transport ATPase and of calmodulin-regulated functions. Biochem Biophys Res Commun. 1981 Jul 30;101(2):418–425. doi: 10.1016/0006-291x(81)91276-6. [DOI] [PubMed] [Google Scholar]
- Haga N., Forte M., Ramanathan R., Saimi Y., Takahashi M., Kung C. Purification of a soluble protein controlling ca channel activity in paramecium. Biophys J. 1984 Jan;45(1):130–132. doi: 10.1016/S0006-3495(84)84136-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hagiwara S., Ozawa S., Sand O. Voltage clamp analysis of two inward current mechanisms in the egg cell membrane of a starfish. J Gen Physiol. 1975 May;65(5):617–644. doi: 10.1085/jgp.65.5.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hennessey T. M., Kung C. An anticalmodulin drug, W-7, inhibits the voltage-dependent calcium current in Paramecium caudatum. J Exp Biol. 1984 May;110:169–181. doi: 10.1242/jeb.110.1.169. [DOI] [PubMed] [Google Scholar]
- Hidaka H., Asano M., Tanaka T. Activity-structure relationship of calmodulin antagonists, Naphthalenesulfonamide derivatives. Mol Pharmacol. 1981 Nov;20(3):571–578. [PubMed] [Google Scholar]
- Hidaka H., Sasaki Y., Tanaka T., Endo T., Ohno S., Fujii Y., Nagata T. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, inhibits cell proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354–4357. doi: 10.1073/pnas.78.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hinrichsen R. D., Saimi Y. A mutation that alters properties of the calcium channel in Paramecium tetraurelia. J Physiol. 1984 Jun;351:397–410. doi: 10.1113/jphysiol.1984.sp015252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kung C., Saimi Y. The physiological basis of taxes in Paramecium. Annu Rev Physiol. 1982;44:519–534. doi: 10.1146/annurev.ph.44.030182.002511. [DOI] [PubMed] [Google Scholar]
- Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
- Oertel D., Schein S. J., Kung C. Separation of membrane currents using a Paramecium mutant. Nature. 1977 Jul 14;268(5616):120–124. doi: 10.1038/268120a0. [DOI] [PubMed] [Google Scholar]
- Ogura A., Takahashi K. Artificial deciliation causes loss of calcium-dependent responses in Paramecium. Nature. 1976 Nov 11;264(5582):170–172. doi: 10.1038/264170a0. [DOI] [PubMed] [Google Scholar]
- Schaefer W. H., Hinrichsen R. D., Burgess-Cassler A., Kung C., Blair I. A., Watterson D. M. A mutant Paramecium with a defective calcium-dependent potassium conductance has an altered calmodulin: a nonlethal selective alteration in calmodulin regulation. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3931–3935. doi: 10.1073/pnas.84.11.3931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tamm S. L. Calcium activation of macrocilia in the ctenophore Beroë. J Comp Physiol A. 1988 May;163(1):23–31. doi: 10.1007/BF00611993. [DOI] [PubMed] [Google Scholar]
