The membrane electroporation-induced inward current (I-MEP) in pituitary tumor (GH(3)) 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 mu M), glibenclamide (30 mu M), nor ZD7288 (30 mu M) caused any effects on I-MEP, 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 I-MEP was 35 and 75 mu M, respectively. However, unlike LaCl3, MEM (300 mu M) 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 GH(3) 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 I-MEP in pituitary GH(3) cells. MEM-mediated block of I-MEP in these cells is unlinked to its inhibition of glutamate-induced currents or ATP-sensitive le 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. (C) 2011 Elsevier Inc. All rights reserved.