Korean J Physiol Pharmacol.  2001 Dec;5(6):511-519.

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

Affiliations
  • 1Department 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

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.


MeSH Terms

Animals
Calcium Channels
Calcium*
Diagnosis-Related Groups
Ganglia, Spinal
Mice
Mice, Knockout
Neurons
Nimodipine*
omega-Agatoxin IVA
omega-Conotoxin GVIA
Sensory Receptor Cells
Calcium
Calcium Channels
Nimodipine
omega-Agatoxin IVA
omega-Conotoxin GVIA
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