Swelling-induced K+ fluxes in vascular smooth muscle cells are mediated by charybdotoxin-sensitive K+ channels

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-CI 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 Ba2+ and charybdotoxin (ChTX), a potent inhibitor of Ca2+- and voltage-gated K+ channels. Swelling-induced K+ influx in VSMC was diminished in Ca2+-free medium and in cells loaded with Ca2+ chelator BAPTA, but was not accompanied by detectable elevation of [Ca2+](i). In contrast to Ca2+-induced hyperpolarization of erythrocytes triggered by activation of intermediate conductance Ca2+-gated K+ channels (IKCa), 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 Ba2+- and ChTX-sensitive K+ channels. These channels are distinct from IKCa expressed in erythrocytes. Their molecular origin and systems involved in the swelling-induced Ca-i(2+)-independent signal transduction pathway need further investigation. Copyright (C) 2001 S. Karger AG, Basel.