The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents
Graduate School of Biomedical Sciences; Program in Neuroscience; Department of Physiology; Program in Cellular and Molecular Physiology; Senior Scholars Program
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
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Neuroscience and Neurobiology
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.
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Citation: Neuropharmacology. 2003 Aug;45(2):281-92.
Liu, Liwang; Gonzalez, Pamela K.; Barrett, Curtis F.; and Rittenhouse, Ann R., "The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents" (2003). GSBS Student Publications. 775.