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 (IR) 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 IR. IR was stimulated with BPB and indomethacin and inhibited with TPA. These agents altered IR by a mechanism independent of cAMP, which can also modulate IR. The effects of these modulators are consistent with their actions on arachidonic acid (AA) metabolism in Aplysia nervous system, suggesting AA may constitutively inhibit IR. When ganglia were perfused for 12 hr with medium containing BSA to absorb extracellular fatty acids, IR 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 short-term exposure to exogenous AA was observed, long term exposure to exogenous AA and several other unsaturated fatty acids was accompanied by a decrease in IR.
Carlson
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Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
Levitan
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D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001048:Aplysia; D001095:Arachidonic Acids / Q000378:metabolism*; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000098:Acetophenones; D001095:Arachidonic Acids; D005227:Fatty Acids; D013755:Tetradecanoylphorbol Acetate; C006821:4-bromophenacyl bromide; D011188:Potassium; D007213:Indomethacin