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Vol. 289, Issue 3, 1447-1453, June 1999
Department of Pharmacology and Neuroscience Center, University of
Colorado Health Sciences Center, Denver, Colorado
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.
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