Nimodipine as a potential pharmacological tool for characterizing R-type calcium currents

Nimopidine, one of dihydropyridine derivatives, has been widely used to pharmacologically identify L-type Ca currents. In this study, it was tested if nimodipine is a selective blocker for L-type Ca currents in sensory neurons and heterologous system. In mouse dorsal root ganglion neurons (DRG), low concentrations of nimodipine (< 10 μM), mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by ∼38%. Interestingly, high concentrations of nimodipine (> 10 μM) further reduced the "residual" currents in DRG neurons from α1E knock-out mice, after blocking L-, N- and P/Q-type Ca currents with 10 μM nimodipine, 1 μM ω-conotoxin GVIA and 200 nM ω-agatoxin IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine (> 10 μM) also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and α1B and α1E subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine (> 10 μM) is not necessarily selective for L-type Ca currents. While care should be taken in using nimodipine for pharmacologically defining L-type Ca currents from native macroscopic Ca currents, nimodipine (> 10 μM) could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.

Duke Scholars

Author Seog Oh Physics