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Flufenamic acid blocks depolarizing afterpotentials and phasic firing in rat supraoptic neurones
Author(s) -
GhamariLangroudi Masoud,
Bourque Charles W.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.033589
Subject(s) - depolarization , chemistry , biophysics , membrane potential , hyperpolarization (physics) , flufenamic acid , electrophysiology , afterhyperpolarization , reversal potential , supraoptic nucleus , neuroscience , bursting , medicine , hypothalamus , patch clamp , biology , biochemistry , stereochemistry , nuclear magnetic resonance spectroscopy
Depolarizing afterpotentials (DAPs) that follow action potentials in magnocellular neurosecretory cells (MNCs) are thought to underlie the generation of phasic firing, a pattern that optimizes vasopressin release from the neurohypophysis. Previous work has suggested that the DAP may result from the Ca 2+ ‐dependent reduction of a resting K + conductance. Here we examined the effects of flufenamic acid (FFA), a blocker of Ca 2+ ‐dependent non‐selective cation (CAN) channels, on DAPs and phasic firing using intracellular recordings from supraoptic MNCs in superfused explants of rat hypothalamus. Application of FFA, but not solvent (0.1 % DMSO), reversibly inhibited (IC 50 + 13.8 μ m ; R + 0.97 ) DAPs and phasic firing with a similar time course, but had no significant effects ( P > 0.05 ) on membrane potential, spike threshold and input resistance, nor on the frequency and amplitude of spontaneous synaptic potentials. Moreover, FFA did not affect ( P > 0.05 ) the amplitude, duration, undershoot, or frequency‐dependent broadening of action potentials elicited during the spike trains used to evoke DAPs. These findings suggest that FFA inhibits the DAP by directly blocking the channels responsible for its production, rather than by interfering with Ca 2+ influx. They also support a role for DAPs in the generation of phasic firing in MNCs. Finally, the absence of a depolarization and increased membrane resistance upon application of FFA suggests that the DAP in MNCs may not be due to the inhibition of resting K + current, but to the activation of CAN channels.