Nimodipine as a Potential Pharmacological Tool for Characterizing R-Type Calcium Currents

Nimodipine as a Potential Pharmacological Tool for Characterizing R-Type Calcium Currents

<P> 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 (＜10μM), mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by ∼38%. Interestingly, high concentrations of nimodipine (＞10μM) further reduced the &quot;residual&quot; currents in DRG neurons from α<SUB>1E</SUB> knock-out mice, after blocking L-, N- and P/Q-type Ca currents with 10μM nimodipine, 1μM ω-conotoxin GVIA and 200 nM ω-agatoxin IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine (＞10μM) also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and α<SUB>1B</SUB> and α<SUB>1E</SUB> subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine (＞10μM) 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 (＞10μM) could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.