MODULATION OF NEURONAL CALCIUM CHANNELS BY ARACHIDONIC-ACID AND RELATED SUBSTANCES

Low-voltage-activated (l-v-a) and high-voltage-activated (h-v-a) Ca2currents (I-Ca) were recorded in whole-cell voltage clamped NG108-15 n euroblastoma x glioma hybrid cells. We studied the effects of arachido nic acid (AA), oleic acid, myristic acid and of the positively charged compounds tetradecyltrimethyl-ammonium (C(14)TMA) and sphingosine. At pulse potentials >-20 mV, AA (25-100 mu M) decreased l-v-a and h-v-a I-Ca equally. The decrease developed slowly and became continually str onger with increasing time of application. It was accompanied by a sma ll negative shift and a slight flattening of the activation and inacti vation curves of the l-v-a I-Ca. The shift of the activation curve man ifested itself in a small increase of l-v-a I-Ca at pulse potentials < -30 mV. The effects were only partly reversible. The AA effect was not prevented by 50 mu M 5, 8, 11, 14-eicosatetraynoic acid, an inhibitor of the AA metabolism, and not mimicked by 0.1-1 mu M phorbol 12, 13-d ibutyrate, an activator of protein kinase C. Probably, AA directly aff ects the channel protein or its lipid environment. Oleic and myristic acid acted similarly to AA but were much less effective. The positivel y charged compounds C(14)TMA and sphingosine had a different effect: T hey shifted the activation curve of l-v-a I-Ca in the positive directi on and suppressed l-v-a more than h-v-a I-Ca; their effect reached a s teady-state within 5-10 min and was readily reversible. C(14)TMA block ed l-v-a I-Ca with an IC50 of 4.2 mu M while sphingosine was less pote nt.