- Tarr, T.B. et al. (2013) J. Neurosci. 33, 10559.
- Alomone Labs GV-58 increases P/Q-type CaV channel tail currents expressed in Xenopus oocytes.A. Time course of CaV2.1 (co-expressed with α2δ1 and β1 auxiliary subunits) normalized tail current area (see tails in panel B, at the end of the ramp stimulation, back at -100 mV), elicited by 100 ms voltage ramp from holding potential of -100 mV to +50 mV (see panel B, top), delivered every 10 seconds. Application of 20 and 100 µM GV-58 (#G-140) increases the CaV2.1 tail current (periods of application are indicated by the horizontal bars) up to 18 fold, in a reversible manner. B. Representative current traces before and during application of 20 and 100 µM GV-58 as indicated. Note the lack of effect on CaV currents during the ramp stimulation.
GV-58, a Ca2+ channel agonist, is selective for N- (CaV2.2) and P/Q-type (CaV2.1) channels. GV-58 was developed as a modification of (R)-roscovitine, which was previously shown to be a Ca2+ channel agonist. 100 μM GV-58 was originally tested on N-, P/Q-, or L-type channels expressed in tsA-201 cells. GV-58 was shown to be more potent on N- and P/Q Ca2+ channels with an EC50 = 6.8 and 9.9 μM, respectively over L-type calcium channels (EC50 > 100 μM)1. GV-58 slows the closing of the channel, resulting in a large increase in total Ca2+ entry during motor nerve action potential activity.
GV-58 is being tested for the treatment of neuromuscular weakness2.
GV-58 (#G-140) is a highly pure, synthetic, and biologically active compound.
Alomone Labs GV-58 activates presynaptic Ca2+ influx in rat neuronal cells.Representative whole cell recordings of evoked neurotransmission in cultures treated with vehicle or GV-58 (#G-140).Adapted from Beske, P.H. et al. (2017) Sci. Rep. 7, 15862. with permission of SPRINGER NATURE.