La. Shimoda et al., Inhibition of voltage-gated K+ currents by endothelin-1 in human pulmonaryarterial myocytes, AM J P-LUNG, 281(5), 2001, pp. L1115-L1122
Citations number
39
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Recent studies demonstrate that endothelin-1 (ET-1) constricts human pulmon
ary arteries (PA). In this study, we examined possible mechanisms by which
ET-1 might constrict human PA. In smooth muscle cells freshly isolated from
these arteries, whole cell patch-clamp techniques were used to examine vol
tage-gated K+ (K-V) currents. K-V currents were isolated by addition of 100
nM charybdotoxin and were identified by current characteristics and inhibi
tion by 4-aminopyridine (10 mM). ET-1 (10(-8) M) caused significant inhibit
ion of K-V current. Staurosporine (1 nM), a protein kinase C (PKC) inhibito
r, abolished the effect of ET-1. Rings of human intrapulmonary arteries (0.
8-2 mm OD) were suspended in tissue baths for isometric tension recording.
ET-1-induced contraction was maximal at 10(-8) M, equal to that induced by
K-V channel inhibition with 4-aminopyridine, and attenuated by PKC inhibito
rs. These data suggest that ET-1 constricts human PA, possibly because of m
yocyte depolarization via PKC-dependent inhibition of K-V. Our results are
consistent with data we reported previously in the rat, suggesting similar
mechanisms may be operative in both species.