Overview
- Bourinet, E. et al. (2001) Biophys. J. 81, 79.
- Kimm, T. and Bean, B.P. (2014) J. Neurosci. 34, 9182.
Alomone Labs SNX-482 inhibits CaV2.3 channels heterologously expressed in Xenopus oocytes.CaV2.3 channel subunits co-expressed in Xenopus oocytes. Using TEVC, membrane potential was held at -100 mV. Ba2+ (10 mM) currents via CaV2.3 channels were elicited by 40 ms long voltage ramps from -100 to +60 mV, delivered every 10 seconds. Left: Representative current traces before and following the application of 100, 200 and 400 nM SNX-482 (#RTS-500), as indicated. Right: Dose-response for SNX-482 (n = 2-6).
SNX-482 is a peptidyl toxin originally isolated from venom of the spider Hysterocrates gigas. Native SNX-482 blocks specifically CaV2.3 (α1E, R-type) channels1 in a voltage-dependent manner. The block is reversible only upon application of strong voltage to facilitate unbinding.2 SNX-482 inhibits human CaV2.3 channels stably expressed in a mammalian cell line. An IC50 of 15-30 nM was obtained for block of CaV2.3 channel, using either patch clamp electrophysiology or K+-evoked Ca2+ flux. At low nanomolar concentrations, SNX-482 also blocked a native R-type Ca2+ current in rat neurohypophyseal nerve terminals, but concentrations of 200-500 nM had no effect on R-type Ca2+ currents in several types of rat central neurons.1 SNX-482 was also used to demonstrate the contribution of CaV2.3 channels to transmitter release.3 Recently it was shown that higher concentrations of SNX-482 also block CaV2.1 channels in chromaffin cells.4
SNX-482 was found to be the most potent blocker to date for KV4.3 channel with IC50 < 3 nM5.
Alomone Labs Nifedipine and SNX-482 block L-type and R-type CaV channels respectively in rat pancreatic INS-1 832/13 β-cells.Representative CaV currents from INS-1 832/13 cells before and after treatment with Nifedipine (#N-120), a general L-type CaV channel blocker and SNX-482 (#RTS-500), a CaV2.3 channel blocker. 52% of the currents were blocked by Nifedipine (n = 8; p < 0.05) while 31% (n = 10; p < 0.001) of currents were blocked by SNX-482. Cells were held at −70 mV for 2 min after formation of whole-cell mode, and currents elicited by stepped 300 or 500 millisecond depolarizations in 10 mV increments.Adapted from Xie, L. et al. (2016) PLoS ONE 11, e0147862. with permission of PLoS.
