Chronic hypoxia alters effects of endothelin and angiotensin on K+ currents in pulmonary arterial myocytes.
We tested the hypothesis that chronic hypoxia alters the regulation of K+ channels in intrapulmonary arterial smooth muscle cells (PASMCs). Charybdotoxin-insensitive, 4-aminopyridine-sensitive voltage-gated K+ (K(V,CI)) and Ca2+-activated K+ (KCa) currents were measured in freshly isolated PASMCs from rats exposed to 21 or 10% O2 for 17-21 days. In chronically hypoxic PASMCs, K(V, CI) current was reduced and KCa current was enhanced. 4-Aminopyridine (10 mM) depolarized both normoxic and chronically hypoxic PASMCs, whereas charybdotoxin (100 nM) had no effect in either group. The inhibitory effect of endothelin (ET)-1 (10(-7) M) on K(V,CI) current was significantly reduced in PASMCs from chronically hypoxic rats, whereas inhibition by angiotensin (ANG) II (10(-7) M) was enhanced. Neither ET-1 nor ANG II altered K(Ca) current in normoxic PASMCs; however, both stimulated K(Ca) current at positive potentials in chronically hypoxic PASMCs. These results suggest that although modulation of K(V,CI) and KCa channels by ET-1 and ANG II is altered by chronic hypoxia, the role of these channels in the regulation of resting membrane potential was not changed.
Shimoda
L A
LA
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21224, USA.
Sylvester
J T
JT
Sham
J S
JS
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D004553:Electric Conductivity; D019332:Endothelin-1 / Q000494:pharmacology*; D006352:Heart Ventricles; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D015221:Potassium Channels; D000804:Angiotensin II