Hyaluronan export through plasma membranes depends on concurrent K+ efflux by K(ir) channels.
Hyaluronan is synthesized within the cytoplasm and exported into the extracellular matrix through the cell membrane of fibroblasts by the MRP5 transporter. In order to meet the law of electroneutrality, a cation is required to neutralize the emerging negative hyaluronan charges. As we previously observed an inhibiting of hyaluronan export by inhibitors of K(+) channels, hyaluronan export was now analysed by simultaneously measuring membrane potential in the presence of drugs. This was done by both hyaluronan import into inside-out vesicles and by inhibition with antisense siRNA. Hyaluronan export from fibroblast was particularly inhibited by glibenclamide, ropivacain and BaCl(2) which all belong to ATP-sensitive inwardly-rectifying K(ir) channel inhibitors. Import of hyaluronan into vesicles was activated by 150 mM KCl and this activation was abolished by ATP. siRNA for the K(+) channels K(ir)3.4 and K(ir)6.2 inhibited hyaluronan export. Collectively, these results indicated that hyaluronan export depends on concurrent K(+) efflux.
Münster University Hospital, Institute of Physiological Chemistry and Pathobiochemistry, Münster, Germany.
Daniel
D
Hagenfeld
Beatrice
B
Borkenhagen
Tobias
T
Schulz
Hermann
H
Schillers
Udo
U
Schumacher
Peter
P
Prehm
D000577:Amides / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts; D014453:Glucuronosyltransferase / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011189:Potassium Chloride; D016372:RNA, Antisense / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077212:Ropivacaine; D022161:Transport Vesicles / Q000378:metabolism
D000577:Amides; D017609:Barium Compounds; D002712:Chlorides; D017931:DNA Primers; D024661:Potassium Channels, Inwardly Rectifying; D016372:RNA, Antisense; D034741:RNA, Small Interfering; C024986:barium chloride; D011189:Potassium Chloride; D000077212:Ropivacaine; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D011188:Potassium; D005905:Glyburide