Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst.
Granulocytes generate a "respiratory burst" of NADPH oxidase-dependent superoxide anion (O(2)(-*)) production that is required for efficient clearance of bacterial pathogens. Hv1 mediates a voltage-gated H(+) channel activity that is proposed to serve a charge-balancing role in granulocytic phagocytes such as neutrophils and eosinophils. Using mice in which the gene encoding Hv1 is replaced by beta-Geo reporter protein sequence, we show that Hv1 expression is required for measurable voltage-gated H(+) current in unstimulated phagocytes. O(2)(-*) production is substantially reduced in the absence of Hv1, suggesting that Hv1 contributes a majority of the charge compensation required for optimal NADPH oxidase activity. Despite significant reduction in superoxide production, Hv1(-/-) mice are able to clear several types of bacterial infections.
Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, and Department of Cardiovascular Research, Manton Center for Orphan Disease, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA.
I Scott
IS
Ramsey
Evelyne
E
Ruchti
J Stefan
JS
Kaczmarek
David E
DE
Clapham
D000818:Animals; D006098:Granulocytes / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism*; D016897:Respiratory Burst / Q000235:genetics; D013481:Superoxides / Q000378:metabolism*
C540876:Hv1 proton channel, mouse; D007473:Ion Channels; D013481:Superoxides; D019255:NADPH Oxidases