GSBS Student Publications

Title

The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents

Student Author(s)

Curtis F. Barrett

GSBS Program

Cell Biology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Neuroscience; Department of Physiology; Program in Cellular and Molecular Physiology; Senior Scholars Program

Date

8-2003

Document Type

Article

Medical Subject Headings

Animals; Calcium Channel Agonists; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Membrane Potentials; Neural Inhibition; Neurons; PC12 Cells; Pyrroles; Rats

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Neuroscience and Neurobiology

Abstract

One strategy for isolating neuronal L-type calcium (Ca(2+)) currents, which typically comprise a minority of the whole cell current in neurons, has been to use pharmacological agents that increase channel activity. This study examines the effects of the benzoyl pyrrole FPL 64176 (FPL) on L-type Ca(2+) currents and compares them to those of the dihydropyridine (+)-202-791. At micromolar concentrations, both agonists increased whole cell current amplitude in PC12 cells. However, FPL also significantly slowed the rate of activation and elicited a longer-lasting slow component of the tail current compared to (+)-202-791. In single channel cell-attached patch recordings, FPL increased open probability, first latency, mean closed time and mean open time more than (+)-202-791, with no difference in unitary conductance. These gating differences suggest that, compared to (+)-202-791, FPL decreases transition rates between open and closed conformations. Where examined, the actions of FPL and (+)-202-791 on whole cell L-type currents in sympathetic neurons appeared similar to those in PC12 cells. In contrast to its effects on L-type current, 10 microM FPL inhibited the majority of the whole cell current in HEK cells expressing a recombinant N-type Ca(2+) channel, raising caution concerning the use of FPL as a selective L-type Ca(2+) channel agonist in neurons.

Rights and Permissions

Citation: Neuropharmacology. 2003 Aug;45(2):281-92.

Comments

Medical student Pamela Gonzalez participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.

Related Resources

Link to article in PubMed

Journal Title

Neuropharmacology

PubMed ID

12842134