Nimodipine as a potential pharmacological tool for characterizing R-type calcium currents.
- Author:
Seog Bae OH
1
Author Information
1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Avenue Searle 7-567, Chicago, IL, 60611, USA. s-oh2@northwestern.edu
- Publication Type:Original Article
- MeSH:
Animals;
Calcium Channels;
Calcium*;
Diagnosis-Related Groups;
Ganglia, Spinal;
Mice;
Mice, Knockout;
Neurons;
Nimodipine*;
omega-Agatoxin IVA;
omega-Conotoxin GVIA;
Sensory Receptor Cells
- From:The Korean Journal of Physiology and Pharmacology
2001;5(6):511-519
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 muM), mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by apprx38%. Interestingly, high concentrations of nimodipine (>10 muM) further reduced the "residual" currents in DRG neurons from alpha1E knock-out mice, after blocking L-, N- and P/Q-type Ca currents with 10 muM nimodipine, 1 muM omega-conotoxin GVIA and 200 nM omega-agatoxin IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine (>10 muM) also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and alpha1B and alpha1E subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine (>10 muM) 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 muM) could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.
