PMID- 12456832
OWN - NLM
STAT- MEDLINE
DCOM- 20030616
LR  - 20190513
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 545
IP  - 2
DP  - 2002 Dec 1
TI  - Flufenamic acid blocks depolarizing afterpotentials and phasic firing in rat 
      supraoptic neurones.
PG  - 537-42
AB  - 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 microM; 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.
FAU - Ghamari-Langroudi, Masoud
AU  - Ghamari-Langroudi M
AD  - Centre for Research in Neuroscience, Montreal General Hospital & McGill 
      University, 1650 Cedar Avenue, Montreal, QC, Canada H3G 1A4.
FAU - Bourque, Charles W
AU  - Bourque CW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Ion Channels)
RN  - 60GCX7Y6BH (Flufenamic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Calcium/physiology
MH  - Electric Stimulation
MH  - Electrophysiology
MH  - Flufenamic Acid/*pharmacology
MH  - In Vitro Techniques
MH  - Ion Channels/drug effects/physiology
MH  - Male
MH  - Membrane Potentials/drug effects/physiology
MH  - Microelectrodes
MH  - Neurons/*drug effects
MH  - Patch-Clamp Techniques
MH  - Pituitary Gland, Posterior/drug effects/physiology
MH  - Rats
MH  - Rats, Long-Evans
MH  - Supraoptic Nucleus/cytology/*drug effects
MH  - Synaptic Transmission/drug effects/physiology
PMC - PMC2290680
EDAT- 2002/11/29 04:00
MHDA- 2003/06/17 05:00
PMCR- 2003/12/01
CRDT- 2002/11/29 04:00
PHST- 2002/11/29 04:00 [pubmed]
PHST- 2003/06/17 05:00 [medline]
PHST- 2002/11/29 04:00 [entrez]
PHST- 2003/12/01 00:00 [pmc-release]
AID - PHY_033589 [pii]
AID - 10.1113/jphysiol.2002.033589 [doi]
PST - ppublish
SO  - J Physiol. 2002 Dec 1;545(2):537-42. doi: 10.1113/jphysiol.2002.033589.