title: Characterization of the K+ (Na+)/H+ monovalent cation exchanger in the human red blood cell membrane: effects of transport inhibitors.
abstract: The (ouabain + bumetanide + EGTA)-insensitive K+ influx (defined as residual K+ influx) in the human erythrocyte was investigated with respect to the characterization of the recently identified K+(Na+)/H+ exchanger (Richter et al. 1997). In particular, the effects of selected ion transport inhibitors on this flux in physiological ionic strength (high ionic strength, HIS) as well as low ionic strength (LIS) solutions were qstudied. The stimulation of the K+ influx observed in LIS medium was further enhanced when DIDS, phloretin, eosin-5-maleimide, furosemide, DIOA, NPPB, or DCDPC was present at a concentration of 0.1 mmol/l. This paradoxical, inhibitor-induced increase of the K+ influx was more pronounced in LIS media where chloride (7.5 mmol/l) was replaced by nitrate. For DNDS, niflumic acid, and MK-196 (0.1 mmol/l) an enhanced K+ transport could only be observed in nitrate-containing LIS solution. Bumetanide and purine riboside, at a concentration of 0.1 mmol/l, did not cause significant changes of the K+ influx in either chloride- or nitrate-containing LIS media. Dipyridamole and ruthenium red (0.1 mmol/l), which are positively charged, significantly reduced the K+ influx in both chloride- and nitrate-containing LIS media. In nitrate-containing HIS solution only dipyridamole inhibited the K+ influx. The residual K+ influx in LIS solution was significantly increased by removing internal [Mg2+], and decreased by quinacrine (1 mmol/l). In HIS solution, no effect of altering intracellular Mg2+ occurred but a stimulation of the flux by quinacrine was observed. The results are discussed in terms of a more general surface charge effect of the used inhibitors on the K+(Na+)/H+ exchanger.
authors.affiliation: Biophysics Section, Institute of Biology, Humboldt University Berlin, Germany. Ingolf=Bernhardt@rz.hu-berlin.de
authors.forename: I
authors.initials: I
authors.lastname: Bernhardt
authors.forename: A Y
authors.initials: AY
authors.lastname: Bogdanova
authors.forename: D
authors.initials: D
authors.lastname: Kummerow
authors.forename: K
authors.initials: K
authors.lastname: Kiessling
authors.forename: J
authors.initials: J
authors.lastname: Hamann
authors.forename: J C
authors.initials: JC
authors.lastname: Ellory
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000494:pharmacology; D007192:Indenes / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D012016:Reference Values; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C059990:((dihydroindenyl)oxy)alkanoic acid; D002264:Carboxylic Acids; D004232:Diuretics; D004791:Enzyme Inhibitors; D007189:Indans; D007192:Indenes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017923:Sodium-Hydrogen Exchangers; D004176:Dipyridamole; D005665:Furosemide; C013352:indacrinone; D011796:Quinacrine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid