In this study, using whole cell and single-channel configurations of t
he patch-clamp technique, we characterized K+ currents (I-K) in cultur
ed human pulmonary arterial smooth muscle cells. The net whole cell ou
tward membrane current (I-Ko) was activated at potentials positive to
-60 mV. One component of I-Ko, I-K(dr), was inhibited by 4-aminopyridi
ne (4-AP) and high concentrations of tetraethylammonium (TEA) but was
Ca2+ and charybdotoxin (CTX) insensitive. The other component of I-Ko,
I-K(Ca), was voltage and Ca2+ dependent and was inhibited by CTX and
low concentrations of TEA. Activation of I-Ko in single-channel record
ings was voltage dependent and demonstrated a high-conductance channel
(245 +/- 2 pS) that was Ca2+ and CTX sensitive [I-K(Ca)] and a low-co
nductance channel (109 +/- 2 pS) that was inhibited by 4-AP [I-K(dr)]
but was insensitive to low concentrations of TEA or to an increase in
intracellular [Ca2+]. In isolated pulmonary arterial rings, TEA and 4-
AP caused an additive increase in arterial tension. To our knowledge t
hese data provide the first characterization of the I-K in human pulmo
nary arterial smooth muscle cells and indicate that I-K(Ca), and I-K(d
r) play an important role in maintaining pulmonary vascular tone. The
data confirm previous observations in pulmonary smooth muscle cells of
animal models.