Modulation of neuronal calcium channels by arachidonic acid and related substances

Low-voltage-activated (l-v-a) and high-voltage-activated (h-v-a) Ca2+ currents (ICa) were recorded in whole-cell voltage clamped NG108-15 neuroblastoma x glioma hybrid cells. We studied the effects of arachidonic acid (AA), oleic acid, myristic acid and of the positively charged compounds tetradecyltrimethylammonium (C14TMA) and sphingosine. At pulse potentials > -20 mV, AA (25-100 microM) decreased l-v-a and h-v-a ICa equally. The decrease developed slowly and became continually stronger with increasing time of application. It was accompanied by a small negative shift and a slight flattening of the activation and inactivation curves of the l-v-a ICa. The shift of the activation curve manifested itself in a small increase of l-v-a ICa at pulse potentials < -30 mV. The effects were only partly reversible. The AA effect was not prevented by 50 microM 5, 8, 11, 14-eicosatetraynoic acid, an inhibitor of the AA metabolism, and not mimicked by 0.1-1 microM phorbol 12, 13-dibutyrate, an activator of protein kinase C. Probably, AA directly affects the channel protein or its lipid environment. Oleic and myristic acid acted similarly to AA but were much less effective. The positively charged compounds C14TMA and sphingosine had a different effect: They shifted the activation curve of l-v-a ICa in the positive direction and suppressed l-v-a more than h-v-a ICa; their effect reached a steady-state within 5-10 min and was readily reversible. C14TMA blocked l-v-a ICa with an IC50 of 4.2 microM while sphingosine was less potent.