Arachidonic acid reversibly enhances N-type calcium current at an extracellular site

We examined the effects of arachidonic acid (AA) on whole cell Ca2+ channel activity in rat superior cervical ganglion neurons. Our companion paper (L iu L, Barrett CF, and Rittenhouse AR. Am J Physiol Cell Physiol 280: C1293- C1305, 2001) demonstrates that AA induces several effects, including enhanc ement of current amplitude at negative voltages, and increased activation k inetics. This study examines the mechanisms underlying these effects. First , enhancement is rapidly reversible by bath application of BSA. Second, enh ancement appears to occur extracellularly, since intracellular albumin was without effect on enhancement, and bath-applied arachidonoyl coenzyme A, an amphiphilic AA analog that cannot cross the cell membrane, mimicked enhanc ement. In addition, enhancement is voltage dependent, in that currents were enhanced to the greatest degree at -10 mV, whereas virtually no enhancemen t occurred positive of +30 mV. We also demonstrate that AA-induced increase s in activation kinetics are correlated with enhancement of current amplitu de. An observed increase in the voltage sensitivity may underlie these effe cts. Finally, the majority of enhancement is mediated through N-type curren t, thus providing the first demonstration that this current type can be enh anced by AA.