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Research ArticleArticle

Block by Ruthenium Red of Cloned Neuronal Voltage-Gated Calcium Channels

Susan M. Cibulsky and William A. Sather
Journal of Pharmacology and Experimental Therapeutics June 1999, 289 (3) 1447-1453;
Susan M. Cibulsky
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William A. Sather
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Abstract

The dye ruthenium red (RuR) has diverse experimental uses, including block of ion channels. RuR is a well described antagonist of one class of intracellular Ca2+ release channels, the ryanodine receptors, but recently this compound has also been identified as a putative blocker of voltage-gated calcium channels of the surface membrane involved in neurotransmitter release. Using electrophysiological methods, we have studied the action of RuR upon pure populations of neuronal voltage-gated ion channels heterologously expressed in Xenopus laevis oocytes. All four channel types studied, including class A (P/Q-type), class B (N-type), class C (L-type), and class E channels, are sensitive to RuR, with IC50 values ranging from 0.7 to 67.1 μM. Block of class C and class E channels most likely results from 1:1 binding of ruthenium red at a site in the extracellular entrance to the pore, resulting in obstruction of permeant ion flux through these channels. The mechanism of block of class A and class B channels is more complex, requiring binding of more than one molecule of RuR per channel.

Footnotes

  • Send reprint requests to: Dr. William A. Sather, Neuroscience Center, B-138, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262. E-mail:william.sather{at}uchsc.edu

  • ↵1 This work was supported by National Institutes of Health Grants AG04418 and NS35245, and the American Federation for Aging Research Grant A96079.

  • Abbreviations:
    RuR
    ruthenium red
    • Received December 10, 1998.
    • Accepted February 11, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 3
1 Jun 1999
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Research ArticleArticle

Block by Ruthenium Red of Cloned Neuronal Voltage-Gated Calcium Channels

Susan M. Cibulsky and William A. Sather
Journal of Pharmacology and Experimental Therapeutics June 1, 1999, 289 (3) 1447-1453;

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Research ArticleArticle

Block by Ruthenium Red of Cloned Neuronal Voltage-Gated Calcium Channels

Susan M. Cibulsky and William A. Sather
Journal of Pharmacology and Experimental Therapeutics June 1, 1999, 289 (3) 1447-1453;
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