Constant turnover of arachidonic acid and inhibition of a potassium current in Aplysia giant neurons

Steady-state currents at hyperpolarized membrane potentials were studied in the homologous giant neurons, LP1 and R2, of Aplysia using two-electrode voltage clamp. Nearly half of the steady-state current at voltages more hyperpolarized than −70 mV had characteristics similar to the inwardly rectifying potassium current ( I R ) described previously in Aplysia neurons. The pharmacological agents 4-bromophenacylbromide, indomethacin, and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate were found to modulate I R . I R was stimulated with BPB and indomethacin and inhibited with TPA. These agents altered I R by a mechanism independent of c AMP, which can also modulate I R . The effects of these modulators are consistent with their actions on arachidonic acid (AA) metabolism in Aplysia nervous system, suggesting AA may constitutively inhibit I R . When ganglia were perfused for 12 hr with medium containing BSA to absorb extracellular fatty acids, I R was increased nearly twofold. This increase was partially inhibited by addition of AA to the perfusion medium, and completely inhibited by pretreatment of ganglia with BPB. Although no direct effect of shortterm exposure to exogenous AA was observed, long term exposure to exogenous AA and several other unsaturated fatty acids was accompanied by a decrease in I R .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48022/1/232_2005_Article_BF01868465.pd