title: Swelling-induced K(+) fluxes in vascular smooth muscle cells are mediated by charybdotoxin-sensitive K(+) channels.
abstract: This study examines the relative contributions of K-Cl cotransport and K(+) channels to swelling-induced K(+) fluxes in vascular smooth muscle cells (VSMC). DIOA known as a potent inhibitor of erythrocyte K-Cl cotransport exerts diverse side-effects on VSMC and can not be used to analyze the role of this carrier in swelling-induced K(+) fluxes. Other inhibitors of K-Cl cotransport (furosemide, okadaic acid and calyculin A) did not affect K(+) fluxes in VSMC triggered by swelling. Swelling-induced K(+) fluxes in VSMC were also not affected by K(+) channel blockers such as TEA, glibenclamide and apamin, but were blocked by Ba(2+) and charybdotoxin (ChTX), a potent inhibitor of Ca(2+)- and voltage-gated K(+) channels. Swelling-induced K(+) influx in VSMC was diminished in Ca(2+)-free medium and in cells loaded with Ca(2+) chelator BAPTA, but was not accompanied by detectable elevation of [Ca(2+)](i). In contrast to Ca(2+)-induced hyperpolarization of erythrocytes triggered by activation of intermediate conductance Ca(2+)-gated K(+) channels (IK(Ca)), neither clotrimazole nor calmodulin antagonists (R24571, trifluoroperazine, fluphenazine) affected swelling-induced K(+) influx in VSMC. In conclusion, K(+) fluxes triggered in swollen VSMC are mediated by Ba(2+)- and ChTX-sensitive K(+) channels. These channels are distinct from IK(Ca) expressed in erythrocytes. Their molecular origin and systems involved in the swelling-induced Ca(2+)(i)-independent signal transduction pathway need further investigation.
authors.affiliation: Lab. of Biomembranes, Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Anfinogenova
authors.forename: X
authors.initials: X
authors.lastname: Rodriguez
authors.forename: R
authors.initials: R
authors.lastname: Grygorczyk
authors.forename: N C
authors.initials: NC
authors.lastname: Adragna
authors.forename: P K
authors.initials: PK
authors.lastname: Lauf
authors.forename: P
authors.initials: P
authors.lastname: Hamet
authors.forename: S N
authors.initials: SN
authors.lastname: Orlov
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D048429:Cell Size / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D003470:Culture Media; D004912:Erythrocytes / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats
chemical_list: D002147:Calmodulin; D002712:Chlorides; D003470:Culture Media; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D011188:Potassium; D002118:Calcium