Arachidonic acid both inhibits and enhances whole cell calcium currents inrat sympathetic neurons

We recently reported that arachidonic acid (AA) inhibits L- and N-type Ca2 currents at positive test potentials in the presence of the dihydropyridin e L-type Ca2+ channel agonist (+)-202-791 in dissociated neonatal rat super ior cervical ganglion neurons [Liu L and Rittenhouse AR. J Physiol (Lond) 5 25: 291-404, 2000]. In this first of two companion papers, we characterized the mechanism of inhibition by AA at the whole cell level. In the presence of either omega -conotoxin GVIA or nimodipine, AA decreased current amplit ude, confirming that L- and N-type currents, respectively, were inhibited. AA-induced inhibition was concentration dependent and reversible with an al bumin-containing wash solution, but appears independent of AA metabolism an d G protein activity. In characterizing inhibition, an AA-induced enhanceme nt of current amplitude was revealed that occurred primarily at negative te st potentials. Cell dialysis with albumin minimized inhibition but had litt le effect on enhancement, suggesting that AA has distinct sites of action. We examined AA's actions on current kinetics and found that AA increased ho lding potential-dependent inactivation. AA also enhanced the rate of N-type current activation. These findings indicate that AA causes multiple change s in sympathetic Ca2+ currents.