HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hinkle, P. M. Articles by Osterhoudt, K. C. Search for Related Content PubMed PubMed Citation Articles by Hinkle, P. M. Articles by Osterhoudt, K. C. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 262, Issue 34, 16333-16337, Dec, 1987

Cadmium uptake and toxicity via voltage-sensitive calcium channels

PM Hinkle, PA Kinsella and KC Osterhoudt
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York 14642.

The mechanism of cellular uptake of cadmium, a highly toxic metal ion, is not known. We have studied cadmium uptake and toxicity in an established secretory cell line, GH4C1, which has well characterized calcium channels. Nimodipine, an antagonist of voltage-sensitive calcium channels, protected cells against cadmium toxicity by increasing the LD50 for CdCl2 from 15 to 45 microM, whereas the calcium channel agonist BAY K8644 decreased the LD50. Organic calcium channel blockers of three classes protected cells from cadmium toxicity at concentrations previously shown to block high K+-induced 45Ca2+ influx and secretion. Half-maximal protective effects were obtained at 20 nM nifedipine, 4 microM verapamil, and 7 microM diltiazem. Increasing the extracellular calcium concentration from 20 microM to 10 mM also protected cells from cadmium by causing a 5-fold increase in the LD50 for CdCl2. Neither the calcium channel antagonist nimodipine nor the agonist BAY K8644 altered intracellular metallothionein concentrations, while cadmium caused a 9-20-fold increase in metallothionein over 18 h. Cadmium was a potent blocker of depolarization-stimulated 45Ca2+ uptake (IC50 = 4 microM), and the net uptake of cadmium measured with 109Cd2+ was less than 0.3% that of calcium. Although the rate of cadmium uptake was low relative to that of calcium, entry via voltage-sensitive calcium channels appeared to account for a significant portion of cadmium uptake; 109Cd2+ uptake at 30 min was increased 57% by high K+/BAY K8644, which facilitates entry through channels. Furthermore, calcium channel blockade with 100 nM nimodipine decreased total cell 109Cd2+ accumulation after 24 h by 63%. These data indicate that flux of cadmium through dihydropyridine-sensitive, voltage-sensitive calcium channels is a major mechanism for cadmium uptake by GH4C1 cells, and that pharmacologic blockade of calcium channels can afford dramatic protection against cadmium toxicity.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Cosio, E. Martinoia, and C. Keller Hyperaccumulation of Cadmium and Zinc in Thlaspi caerulescens and Arabidopsis halleri at the Leaf Cellular Level Plant Physiology, February 1, 2004; 134(2): 716 - 725. [Abstract] [Full Text] [PDF]

				S. Peng, R. K. Hajela, and W. D. Atchison Effects of Methylmercury on Human Neuronal L-Type Calcium Channels Transiently Expressed in Human Embryonic Kidney Cells (HEK-293) J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 424 - 432. [Abstract] [Full Text] [PDF]

				F.-J. Zhao, R. E. Hamon, E. Lombi, M. J. McLaughlin, and S. P. McGrath Characteristics of cadmium uptake in two contrasting ecotypes of the hyperaccumulator Thlaspi caerulescens J. Exp. Bot., March 1, 2002; 53(368): 535 - 543. [Abstract] [Full Text] [PDF]

				T. Yanagiya, N. Imura, S. Enomoto, Y. Kondo, and S. Himeno Suppression of a High-Affinity Transport System for Manganese in Cadmium-Resistant Metallothionein-Null Cells J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1080 - 1086. [Abstract] [Full Text]

				E. C. Foulkes Transport of Toxic Heavy Metals Across Cell Membranes Experimental Biology and Medicine, March 1, 2000; 223(3): 234 - 240. [Abstract] [Full Text]

				M. A. Khoyi, L. G. Gregory, A. D. Smith, K. D. Keef, and D. P. Westfall An Unusual Ca2+ Entry Pathway Activated by Protein Kinase C in Dog Splenic Artery J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 823 - 828. [Abstract] [Full Text]

				L. E. Kerper and P. M. Hinkle Cellular Uptake of Lead Is Activated by Depletion of Intracellular Calcium Stores J. Biol. Chem., March 28, 1997; 272(13): 8346 - 8352. [Abstract] [Full Text] [PDF]