Diphenyleneiodonium inhibits both potassium and calcium currents in isolated pulmonary artery smooth muscle cells.
Diphenyleneiodonium (DPI) blocks hypoxic vasoconstriction in the pulmonary vasculature. Because one of the actions of DPI is the inhibition of NADPH oxidase, this has led to the suggestion that NADPH oxidase acts as an oxygen tension sensor in pulmonary smooth muscle cells. We investigated the effects of DPI on potassium and calcium currents in freshly isolated pulmonary artery smooth muscle cells by using whole cell patch-clamp recordings, since these ionic currents are known to be involved in hypoxic pulmonary vasoconstriction. DPI (3 and 10 microM) reversibly inhibited potassium currents, and in its presence, residual currents appeared markedly more transient than under control conditions. The actions of DPI could not be reversed by 4.4 mM hydrogen peroxide, the product of NADPH oxidase. Calcium channel currents were also reversibly inhibited by 3 microM DPI. Thus DPI is a nonselective blocker of ionic channels in pulmonary smooth muscle cells, and its mechanism of action does not appear to involve inhibition of hydrogen peroxide formation. The ability of DPI to block calcium currents can explain its inhibition of hypoxic pulmonary vasoconstriction.
Weir
E K
EK
Department of Pharmacology, Leeds University, United Kingdom.
Wyatt
C N
CN
Reeve
H L
HL
Huang
J
J
Archer
S L
SL
Peers
C
C
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000502:physiology
D002121:Calcium Channel Blockers; D009861:Onium Compounds; D015221:Potassium Channels; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases