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

Abstract

Steady-state currents at hyperpolarized membrane potentials were studied in the homologous giant neurons, LP1 and R2, ofAplysia 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 inAplysia neurons. The pharmacological agents 4-bromophenacylbromide, indomethacin, and the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate were found to modulateI _R.I _R was stimulated with BPB and indomethacin and inhibited with TPA. These agents alteredI _R by a mechanism independent ofcAMP, which can also modulateI _R. The effects of these modulators are consistent with their actions on arachidonic acid (AA) metabolism inAplysia nervous system, suggesting AA may constitutively inhibitI _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 inI _R.