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Circ Res. 1994 Jul;75(1):144-8.

Selective inhibition of T-type Ca2+ channels by Ro 40-5967.

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Oregon Regional Primate Research Center, Beaverton 97006.


The present study shows that the chemically novel nondihydropyridine Ca2+ antagonist, Ro 40-5967, blocks T-type divalent ion currents in vascular muscle cells. T-type Ca2+ channels were blocked selectively and completely by therapeutic concentrations of 1 to 10 mumol/L Ro 40-5967, at which there was only 25% to 70% block of L-type Ca2+ currents. Using the combination of Ro 40-5967 and nisoldipine, a dihydropyridine selective for L-type Ca2+ channels, we found that all Ca2+ current could be completely blocked; thus, Ro 40-5967 is the first Ca2+ channel blocker to eliminate dihydropyridine-insensitive voltage-dependent Ca2+ current at therapeutically useful concentrations. The stepwise sequential block of T- and L-type Ca2+ currents demonstrated in the present study fulfills the functional criterion for the separate identity of the two Ca2+ channel types, and introduces a pharmacological tool that promises to be important in the exploration of T-type Ca2+ channel function.

[Indexed for MEDLINE]

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