Block by ruthenium red of cloned neuronal voltage-gated calcium channels.
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 microM. 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.
Cibulsky
S M
SM
Department of Pharmacology and Neuroscience Center, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Sather
W A
WA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020746:Calcium Channels, L-Type; D003001:Cloning, Molecular; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology*; D014158:Transcription, Genetic; D014982:Xenopus laevis
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D011994:Recombinant Proteins; D012430:Ruthenium Red