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

Publication Date

2003-8

UMMS Affiliation

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

Document Type

Article

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.

DOI of Published Version

10.1016/S0028-3908(03)00153-9

Source

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

Journal/Book/Conference Title

Neuropharmacology

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

PubMed ID

12842134

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