Flufenamic Acid Affects Multiple Currents and Causes Intracellular Ca 2+ Release in Aplysia Bag Cell Neurons

• Published in: Journal of neurophysiology 2008-07, Vol.100 (1), p.38-49
• Main Authors: Gardam, Kate E., Geiger, Julia E., Hickey, Charlene M., Hung, Anne Y., Magoski, Neil S.
• Format: Article
• Language: English
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.90265.2008

Flufenamic acid (FFA) is a nonsteroidal antiinflammatory agent, commonly used to block nonselective cation channels. We previously reported that FFA potentiated, rather than inhibited, a cation current in Aplysia bag cell neurons. Prompted by this paradoxical result, the present study examined the effects of FFA on membrane currents and intracellular Ca 2+ in cultured bag cell neurons. Under whole cell voltage clamp, FFA evoked either outward ( I out ) or inward ( I in ) currents. I out had a rapid onset, was inhibited by the K + channel blocker, tetraethylammonium, and was associated with both an increase in membrane conductance and a negative shift in the whole cell current reversal potential. I in developed more slowly, was inhibited by the cation channel blocker, Gd 3+ , and was concomitant with both an increased conductance and positive shift in reversal potential. FFA also enhanced the use-dependent inactivation and caused a positive-shift in the activation curve of the voltage-dependent Ca 2+ current. Furthermore, as measured by ratiometric imaging, FFA produced a rise in intracellular Ca 2+ that persisted in the absence of extracellular Ca 2+ and was reduced by depleting either the endoplasmic reticulum and/or mitochondrial stores. Ca 2+ appeared to be involved in the activation of I in , as strong intracellular Ca 2+ buffering effectively eliminated I in but did not alter I out . Finally, the effects of FFA were likely not due to block of cyclooxygenase given that the general cyclooxygenase inhibitor, indomethacin, failed to evoke either current. That FFA influences a number of neuronal properties needs to be taken into consideration when employing it as a cation channel antagonist.