Potent inhibition of a recombinant low voltage-activated Ca(2+) channel by SB-209712.
T-type Ca(2+) currents were recorded in 2 mM Ca(2+) from HEK293 cells stably expressing the low voltage-activated Ca(2+) channel sub-unit alpha(1I). These currents were inhibited by the known Ca(2+) channel antagonist mibefradil with an IC(50) close to 1 microM. SB-209712 (1,6,bis¿1-[4-(3-phenylpropyl)piperidinyl]¿hexane), a compound originally developed as a high voltage-activated Ca(2+) channel blocker, proved to be a more potent T-type channel antagonist, exhibiting an IC(50) in the region of 500 nM. The antagonism produced by SB-209712 was reversed following drug removal and the observed antagonism exhibited little or no voltage-dependence with respect to either holding or test potential. These data indicate that SB-209712 is amongst the most potent known non-peptide T-type channel antagonists and thus may have some use in understanding the role of these channels in cellular function.
McNaughton
N C
NC
Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, NFSP (North) Third Avenue, Essex, CM19 5AW, Harlow, UK.
Warre
R
R
Cooper
D G
DG
Nasir
S
S
Ranson
J L
JL
Randall
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D020748:Mibefradil / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000187:drug effects
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D010880:Piperidines; D011994:Recombinant Proteins; C417214:SB 209712; D020748:Mibefradil