Nitric oxide activates ATP-dependent K+ channels in human eosinophils.
Nitric oxide (NO) affects the function of ion channels in many cell types, but its role in the regulation of eosinophil ion channels is unknown. In this study, we used the perforated patch-clamp method to investigate the effect of endogenous and exogenous NO on eosinophil ion channels. Using the NO synthase inhibitor, N-nitro-L-arginine methyl ester, we showed that endogenous NO did not affect the whole-cell current in eosinophil. However, two NO donors, S-nitroso-glutathione and S-nitroso-N-acetyl penicillamine, activated whole-cell currents via a NO/cGMP-dependent pathway. Ion substitution and pharmacological studies showed that NO-activated currents were carried by K+ ions, likely through ATP-dependent K+ channels (K(ATP)). Although RT-PCR studies showed the expression of several classes of K+ channels in human eosinophils, NO donors affected only K(ATP) channel function. We conclude that NO, at concentrations likely to be encountered in vivo, could prevent eosinophil activation by opening K(ATP) channels.
Schwingshackl
Andreas
A
Department of Physiology, Pulmonary Research Group, University of Alberta, 7-46 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
Moqbel
Redwan
R
Duszyk
Marek
M
D000255:Adenosine Triphosphate / Q000502:physiology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester