Overview
- Kraus, R.L. et al. (2010) J. Pharmacol. Exp. Ther. 335, 409.
Alomone Labs TTA-A2 blocks T-type CaV channels expressed in Xenopus oocytes.A. Time course of CaV3.2 peak current amplitude, elicited by 100 ms voltage step from holding potential of -100 mV to -30 mV, delivered every 10 seconds. Application of 100 µM TTA-A2 (#T-140) inhibits the CaV3.2 current in a reversible manner (indicated by the horizontal bar). B. Representative current traces before and during application of 100 µM TTA-A2 as indicated.
Alomone Labs TTA-A2 blocks T-type CaV channels expressed in Xenopus oocytes.A. Time course of CaV3.1 peak current amplitude, elicited by 50 ms voltage step from holding potential of -80 mV to -20 mV, delivered every 10 seconds. Application of 1 µM TTA-A2 (#T-140) inhibits the CaV3.1 current in a reversible manner (indicated by the horizontal bar). B. Representative current traces before and during application of 1 µM TTA-A2 as indicated.
Low-voltage-activated (T-type/CaV3) Ca2+ channels are a subclass of voltage-dependent Ca2+ channels allowing Ca2+ entry near the resting potential of most cells1. Various synthetic T-channel blockers have been described in the past few years including TTA-A2, a potent, state-dependent, and highly selective T-type CaV antagonist2.
TTA-A2 was found to inhibit all three subtypes of low-voltage-gated T-type channels (CaV3.1, CaV3.2, and CaV3.3) with comparable potencies. Changing membrane resting potentials from −100 to −80 mV enhanced compound potency ∼40-fold, from an IC50 of ∼4 μM to 0.1 μM, respectively, indicating state dependence of inhibition3. in vivo studies have demonstrated that TTA-A2 reduces absence epilepsy seizures4, pain perception5, nicotine self-administration6 and weight gain7. It also improves the quality of sleep7 and displays antipsychotic properties8.
Alomone Labs TTA-A2 inhibits T-type CaV channels in response to hypoxia.Representative example of sensory nerve response (impulses (imp)/s) to hypoxia in the presence of vehicle or 25 μM TTA-A2 (#T-140), and 5 min after washout (left panel). Effect of TTA-A2 on sensory nerve response to hypoxia (right panel).Adapted from Makarenko, V.V. et al. (2015) Am. J. Physiol. 308, C146. with permission of the American Physiological Society.
