Potent inhibition of a recombinant low voltage-activated Ca2+ channel by SB-209712

T-type Ca2+ currents were recorded in 2 mM Ca2+ from HEK93 cells stably exp ressing the low voltage-activated Ca2+ channel sub-unit alpha (11). These c urrents were inhibited by the known Ca2+ channel antagonist mibefradil with an IC50 close to 1 muM. SB-209712 (1,6,bis{1-[4-(3-phenylpropyl)piperidiny l]}hexane), a compound originally developed as a high voltage-activated Ca2 + channel blocker, proved to be a more potent T-type channel antagonist, ex hibiting an IC50 in the region of 500 nM. The antagonism produced by SB-209 712 was reversed following drug removal and the observed antagonism exhibit ed little or no voltage-dependence with respect to either holding or test p otential. These data indicate that SB-209712 is amongst the most potent kno wn non-peptide T-type channel antagonists and thus may have some use in und erstanding the role of these channels in cellular function. (C) 2000 Elsevi er Science B.V. All rights reserved.