Inhibitory effect of memantine, an NMDA-receptor antagonist, on electoporation-induced inward currents in pituitary GH3 cells

The membrane electroporation-induced inward current (IMEP) in pituitary tumor (GH3) cells was characterized. This current emerges irregularly when membrane hyperpolarizations to −200 mV with a holding potential of −80 mV were elicited. Neither E-4031 (10 μM), glibenclamide (30 μM), nor ZD7288 (30 μM) caused any effects on IMEP. The single-channel conductance and pore radius were estimated to be around 1.12 nS and 1.7 nm, respectively. LaCl3- and memantidine (MEM)-induced block of this current was also examined. The IC50 value for LaCl3- and MEM-induced inhibition of IMEP was 35 and 75 μM, respectively. However, unlike LaCl3, MEM (300 μM) did not exert any effect on voltage-gated Ca2+ current. In inside-out configuration, MEM applied to either external or internal surface of the excised patch did not suppress the activity of ATP-sensitive K+ channels expressed in GH3 cells, although glibenclamide significantly suppressed channel activity. This study provides the first evidence to show that MEM, a non-competitive antagonist of N-methyl D-aspartate receptors, directly inhibits the amplitude of IMEP in pituitary GH3 cells. MEM-mediated block of IMEP in these cells is unlinked to its inhibition of glutamate-induced currents or ATP-sensitive K+ currents. The channel-suppressing properties of MEM might contribute to the underlying mechanisms by which it and its structurally related compounds affect neuronal or neuroendocrine function.

Research highlights
► Membrane electroporation-induced inward current (IMEP) in pituitary tumor (GH3) cells was characterized.
► LaCl3- and Memantidine (MEM)-induced block of this current was examined.
► The IC50 value for MEM-induced inhibition of IMEP was 75 μM.
► MEM did not suppress the activity of ATP-sensitive K+ channels expressed in GH3 cells.
► MEM, an antagonist of N-methyl D-aspartate receptors, directly inhibits IMEP amplitude.