Inhibitory effect of memantine, an NMDA-receptor antagonist, on electroporation-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.
Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan. snwu@mail.ncku.edu.tw
Sheng-Nan
SN
Wu
Hsien-Ching
HC
Huang
Chia-Chen
CC
Yeh
Wei-Hsin
WH
Yang
Yi-Ching
YC
Lo
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D018274:Electroporation; D008559:Memantine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine