Amn. Costa et Bs. Brown, INHIBITION OF M-CURRENT IN CULTURED RAT SUPERIOR CERVICAL-GANGLIA BY LINOPIRDINE - MECHANISM OF ACTION STUDIES, Neuropharmacology, 36(11-12), 1997, pp. 1747-1753
The mechanism involved in the blockade of M-current by linopirdine was
studied in cultured rat superior cervical sympathetic ganglia using w
hole-cell patch clamp recording. The effects of modulators of intracel
lular signal transduction pathways on muscarine-or linopirdine-induced
inhibition of M-current were compared. Intracellular addition of GDP-
beta-S (500 mu M) attenuated M-current block by muscarine (1 mu M) but
not that of linopirdine (10 mu M). Intracellular dialysis of GTP-gamm
a-S (100 mu M) enhanced and prolonged muscarine-induced inhibition of
M-current but had no effect on the activity of linopirdine. Intracellu
lar BAPTA (20 mM) also inhibited the effects of muscarine without affe
cting those of linopirdine. Intracellular application of linopirdine h
ad no effect on either basal M-current amplitude or the ability of lin
opirdine to block M-current when administered extracellularly. These r
esults indicate that M-current inhibition by linopirdine is unlikely t
o be either G-protein-mediated or calcium-mediated or to involve an in
tracellular site of action and are, therefore, consistent with a direc
t block of the M-channel from its extracellular side. (C) 1998 Elsevie
r Science Ltd. All rights reserved.