Smartox/Selective blocker of Ntype calcium channels/08CON01301000/1mg

Whole-cell currents in cultured hippocampal neurons were recorded to investigate the effects of SO-3, a new O-superfamily conopeptide derived from Conus striatus, on voltage-sensitive channels. SO-3 had no effect on voltage-sensitive sodium currents, delayed rectifier potassium currents, and transient outward potassium currents. Similar to the selective N-type calcium channel blocker omega-conotoxin MVIIA (MVIIA), SO-3 could concentration-dependently inhibit the high voltage-activated (HVA) calcium currents (I(Ca)). MVIIA(3 microM), 10 microM nimodipine, and 0.5 microM omega-agatoxin IVA (Aga) could selectively block the N-, L-, and P/Q-type I(Ca), which contributed approximately 32, approximately 38, and approximately 21% of the HVA currents in hippocampal neurons, respectively. About 31% of the total HVA currents were inhibited by 3 microM SO-3. SO-3 (3 microM) and 3 microM MVIIA inhibited the overlapping components of HVA currents, whereas no overlapping component was inhibited by 3 microM SO-3 and 10 microM nimodipine, or by 3 microM SO-3 and 0.5 microM Aga. Also, 3 microM SO-3 had no effect on R-type currents. SO-3 had less inhibitory effects on non-N-type HVA currents than MVIIA at higher concentrations (30 and 100 microM). The inhibitory effects of SO-3 and MVIIA on HVA currents were almost fully reversible. However, the recovery from block by MVIIA was more rapid than recovery from block by SO-3. It is concluded that SO-3 is a new omega-conotoxin selectively targeting N-type voltage-sensitive calcium channels. Considering the significance of N-type calcium channels for pain transduction, SO-3 may have therapeutic potential as a novel analgesic agent.

The effects of a new O-superfamily conotoxin SO3 on sodium and potassium currents were examined in cultured rat hippocampal neurons using the whole-cell patch clamp technique. SO3 caused a concentration-dependent, rapidly developing and reversible inhibition of sodium currents (I(Na)). The IC(50) value for the blockage of I(Na) was calculated to be 0.49 and the Hill coefficient was 1.7. Using electrophysiological and pharmacological protocols, transient A-type potassium currents (I(A)) and delayed rectifiers potassium currents (I(K)) were isolated. SO3 caused a concentration-dependent, and reversible inhibition of I(K). The IC(50) value for the blockage of I(K) was calculated to be 1.6 and the Hill coefficient was 0.6, with no significant effect on I(A). These results indicate that SO3 can selectively inhibit neuronal sodium and potassium currents.Li, Z., et al. (2003) Effect of new O-superfamily conotoxin SO3 on sodium and potassium currents of cultured hippocampal neurons, Brain Res. PMID: 12591132