Transmembrane calcium influx induced by ac electric fields

Exogenous electric fields induce cellular responses including redistributio n of integral membrane proteins, reorganization of microfilament structures , and changes in intracellular calcium ion concentration ([Ca2+](i)). Altho ugh increases in [Ca2+](i) caused by application of direct current electric fields have been documented, quantitative measurements of the effects of a lternating current (ac) electric fields on [Ca2+](i) are lacking and the Ca 2+ pathways that mediate such effects remain to be identified, Using epiflu orescence microscopy, we have examined in a model cell type the [Ca2+](i) r esponse to ac electric fields. Application of a 1 or 10 Hz electric field t o human hepatoma (Hep3B) cells induces a fourfold increase in [Ca2+](i) (fr om 50 nM to 200 nM) within 30 min of continuous field exposure. Depletion o f Ca2+ in the extracellular medium prevents the electric field-induced incr ease in [Ca2+](i), suggesting that Ca2+ influx across the plasma membrane i s responsible for the [Ca2+](i) increase. Incubation of cells with the phos pholipase C inhibitor U73122 does not inhibit ac electric field-induced inc reases in [Ca2+](i), suggesting that receptor-regulated release of intracel lular Ca2+ is not important for this effect. Treatment of cells with either the stretch-activated cation channel inhibitor GdCl3 or the nonspecific ca lcium channel blocker CoCl2 partially inhibits the [Ca2+](i) increase induc ed by ac electric fields, and concomitant treatment with both GdCl3 and CoC l2 completely inhibits the field-induced [Ca2+](i) increase. Since neither Gd3+ nor Co2+ is efficiently transported across the plasma membrane, these data suggest that the increase in [Ca2+](i) induced by ac electric fields d epends entirely on Ca2+ influx from the extracellular medium.