Prostaglandin El induces an inward current in voltage-clamped NG108-15 cells

The aim of this study was to explore the effect of prostaglandin E1 (PGE1) on the membrane current of whole-cell voltage-clamped NG108-15 neuroblastoma x glioma hybrid cells. Perforated patch was used. The membrane current at -70 mV (leakage current) and the current-voltage curve produced by ramp pulses from -70 to 0 mV were recorded; from the I-V curve, the conductance of the leakage current and its reversal potential were determined. Bath application of PGE1 (22 nM-3 microM) produced an inward current accompanied by a reversible conductance increase. The PGE1 effect varied greatly from cell to cell. In a group of 11 differentiated cells, the inward current induced by 0.2 microM PGE1 was on average 171.1 +/- 49.8 pA, the conductance increased 2.66 +/- 0.50-fold and the reversal potential shifted by + 13.2 +/- 4.0 mV. The average values observed with 22 nM and 3 microM PGE1 were similar. The cell-permeable cAMP analog CPT-cAMP (0.5 mM) acted like PGE1. In 9 out of 16 cells, the PGE1 effect did not disappear and was not even noticeably reduced when the NaCl in the bath was replaced by N-methyl-D-glucamine (NMDG). The PGE1 effect was also seen in Ca2(+)-free NMDG bath but vanished when NMDG was replaced by glucose. It is concluded that PGE1, probably acting via intracellular cAMP, opens non-selective cation channels with large pore diameters which allow the passage of big organic cations.