Previous studies have demonstrated several pathways for the sinusoidal
uptake of endogenous and exogenous organic cations, including two dis
tinct organic cation:H+ exchangers and a separate carrier-mediated sys
tem driven by the inside-negative membrane potential, In this study, t
he driving force(s) for the uptake of the endogenous quaternary amine,
choline, were determined in rat liver basolateral plasma membrane (bl
LPM) vesicles, Choline uptake into an osmotically sensitive space was
not stimulated by an outwardly directed H+ or inwardly directed Na+ gr
adient, Instead, an inside-negative K+ diffusion potential stimulated
choline uptake, suggesting the presence of a conductive pathway for ch
oline uptake in blLPM vesicles, Conductive choline uptake was confirme
d by inducing variable changes in the transmembrane potential with ani
ons of different membrane permeability, Choline uptake in blLPM vesicl
es exhibited 1) temperature dependency; 2) trans-stimulation; and 3) s
aturability, with an approximate Michaelis constant (K-m) of 0.34 mmol
/L and maximum velocity (V-max) of 0.45 nmol/mg protein/15 s, Choline
uptake in blLPM vesicles was cis-inhibited by the structurally similar
derivative, hemicholinium-3 and acetylcholine, but not by substrates
for other organic cation transport processes identified in blLPM vesic
les, including thiamine, tetraethylammonium (TEA), tri-n-butyl-methyla
mmonium (TBuMA), and N'-methylnicotinamide (NMN), These findings demon
strate an electrogenic pathway on the sinusoidal membrane for the upta
ke of this essential nutrient and support the existence of multiple pa
thways for the sinusoidal uptake of endogenous and exogenous organic c
ations.