Effect of ruthenium red on voltage-sensitive Ca++ channels.
The organometallic dye, ruthenium red (RR) inhibited Ca++ influx, omega-conotoxin GVIA-sensitive Ca++ binding and Ca(++)-dependent neurotransmitter release in a qualitatively similar manner in rat and chicken synaptosomes and in mammalian neuromuscular preparations, but had no effect on Ca(++)-dependent processes mediated by the dihydropyridine-sensitive Ca++ channel. These effects are specific for the RR complex, as RuCl3 affected neither Ca++ influx, omega-conotoxin GVIA binding nor neurotransmitter release, but did, however, in contrast to RR, displace [3H]nitrendipine from synaptosomes. RR, in a manner similar to omega-conotoxin MVIIC and omega-agatoxin IVA (AgaIVA), also effectively inhibited the response of the rat diaphragm to nerve stimulation and blocked AgaIVA-sensitive Ca++ influx in the rat brain, suggesting a significant interaction at the P-type voltage-sensitive Ca++ channel. These effects of RR suggest that this amino complex affects both the N and the P domain of the Ca++ channel in the chicken brain and both the N- and P-type Ca++ channel which is intimately coupled to the Ca++ influx and neurotransmitter release in rat synaptosomes. Its ability to block all of the Ca++ influx in mammalian brain preparations and to inhibit completely the nerve-stimulated rat neuromuscular junction certainly indicates a significant action at the P-type voltage-sensitive Ca++ channel, similar to omega-conotoxin MVIIC or AgaIVA. RR should prove to be a valuable synthetic, inexpensive tool with which to probe the neuropharmacology of the mammalian neurotransmitter-linked voltage-sensitive Ca++ channels.
Hamilton
M G
MG
Defence Research Establishment Suffield, Alberta, Canada.
Lundy
P M
PM
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002645:Chickens; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D010791:Phrenic Nerve; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000378:metabolism / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D012430:Ruthenium Red; D011188:Potassium