Overview
- Cazorla, O. et al. (2003) Br. J. Pharmacol. 139, 99.
- Chatelain, P. et al. (1994) Eur. J. Pharmacol. 267, 151.
- Romey, G. et al. (1994) Eur. J. Pharmacol. 263, 101.
Alomone Labs SR 33805 oxalate blocks L-type Ca2+ currents in Xenopus oocytes.A. Time course of L-type channel (CaV1.2+α2δ1+β1a) activity before and during applications of 1 μM SR 33805 oxalate (#S-105) as indicated, and upon wash. Holding potential was -80 mV and currents were elicited every 10 seconds by 100 ms ramp to +60 mV. B. Superimposed current traces of L-type currents before and during applications of 1 μM SR 33805 oxalate, taken from the experiment in A.
Two types of voltage-gated Ca2+ channels (VGCC, CaV) are found in most nonexcitable cells, T-type and the L-type Ca2+ channels1-2.
SR 33805, a fantofarone derivative, is a potent Ca2+ channel antagonist3. It binds allosterically to the a1-subunit of L-type Ca2+ channels (Kd = 20 pM), at a site distinct from other types of blockers4. It potently inhibits the Ca2+ channel, and hence prevents Ca2+ influx, in primary mouse cardiac myocytes cultures with IC50 values ranging from 4.1 to 33 nM5.
SR 33805 shows selectivity for vascular smooth muscle, inducing vasorelaxation without producing inotropic or chronotropic effects6. It inhibits PDGF-stimulated smooth muscle cell proliferation and the associated rise in intracellular Ca2+ concentration with IC50 values of 0.2 µM and 0.3 µM, respectively7.
Despite its strong Ca2+-antagonistic properties, SR33805 increases cardiac cell contractile activity as a consequence of its Ca2+-sensitizing effects. These effects are attributable to both an increase in the maximal Ca2+-activated force and a length-dependent Ca2+-sensitization3.
