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• W2139019936 abstract "The large-conductance Ca²⁺-activated K⁺ (BK) channel is activated by both the increase of intracellular Ca²⁺ concentration and membrane depolarization. The BK channel plays crucial roles as a key molecule in the negative feedback mechanism regulating membrane excitability and cellular Ca²⁺ in various cell types. Here, we report that a widely used slow-response voltage-sensitive fluorescent dye, bis(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC₄(3)], is a potent BK channel activator. The application of DiBAC₄(3) at concentrations of 10 nM and higher significantly increased whole-cell BK channel currents in human embryonic kidney 293 cells expressing rat BK channel α and β1 subunits (rBKαβ1). In the presence of 300 nM DiBAC₄(3), the activation voltage of the BK channel current shifted to the negative direction by approximately 30 mV, but the single-channel conductance was not affected. DiBAC₄(3) activated whole-cell rBKαβ1 and rBKαβ4 currents in the same concentration range but partially blocked rBKαβ2 currents. The BK channel α subunit alone and some other types of K⁺ channels examined were not markedly affected by 1 μM DiBAC₄(3). Structure-activity relationship analyses revealed that a set of oxo- and oxoanion-moieties in two 1,3-dialkylbarbituric acids, which are conjugated by oligomethine, is the novel skeleton for the β-subunit-selective BK channel-opening property of DiBAC₄(3) and related oxonol compounds. This conjugated structure may be located stereochemically in one plane. These findings provide a molecular and structural basis for understanding the regulatory mechanism of BK channel activity by an auxiliary β subunit and will be fundamental to the development of β-selective BK channel openers." @default.
• W2139019936 created "2016-06-24" @default.
• W2139019936 creator A5003856941 @default.
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• W2139019936 date "2007-01-05" @default.
• W2139019936 modified "2023-10-15" @default.
• W2139019936 title "Voltage-Sensitive Oxonol Dyes Are Novel Large-Conductance Ca²⁺-Activated K⁺Channel Activators Selective for β1 and β4 but Not for β2 Subunits" @default.
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• W2139019936 doi "https://doi.org/10.1124/mol.106.031146" @default.
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