Biophysical and Pharmacological Characteristics of Native Two-Pore Domain TASK Channels in Rat Adrenal Glomerulosa Cells
Biophysical and Pharmacological Characteristics of Native Two-Pore Domain TASK Channels in Rat Adrenal Glomerulosa Cells
复制标题
大鼠肾上腺肾小球细胞天然双孔结构域 TASK 通道的生物物理和药理学特征
DOI：
10.1007/s00232-005-7012-x
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
D. Lotshaw
中科院分区：
文献类型：
--
作者：
D. Lotshaw
据报道，在大鼠肾小球细胞中表达了双孔结构域K+通道的ASK亚家族的多个基因。为了确定哪些ASK亚型有助于控制静息膜电位的天然渗漏通道，进行了膜片钳研究，以鉴定诊断重组ASK通道亚型的宏观和单一K+电流的生物物理学和药理学特征。结果表明，K+电导（gK+）介导的几乎完全由弱电压依赖性（泄漏）K+通道密切类似的任务-3。泄漏通道表现出一个单一的电导接近预期的任务-3下采用的记录条件下，简短的平均开放时间和电压依赖性的开放概率。细胞外H+诱导gK+的电压非依赖性抑制，表现出56 nM（pH 7.25）的IC 50和希尔系数为0.75。质子通过促进长寿命的闭合状态（τ > 500 ms）来抑制泄漏通道开放概率（Po）。细胞外Zn 2+模拟H+的作用;抑制gK+表现出41 μM的IC 50和1.26的Hill系数，通过促进长寿命的关闭状态来抑制通道门控。0 mV时，钌红（5 μM）对gK+的抑制率为75.6%。细胞外Mg 2+诱导的电压依赖性阻滞gK+，抑制单一电流振幅，而不影响平均开放时间。布比卡因可诱导gK+的电压依赖性阻滞，在−100 mV和40 mV下的IC 50值分别为116 μM和28 μM，两种电位下的Hill系数均为1。氟烷诱导的gK+的电压依赖性刺激主要是通过减少泄漏通道关闭状态的停留时间。
Multiple genes of the TASK subfamily of two-pore domain K+ channels are reported to be expressed in rat glomerulosa cells. To determine which TASK isoforms contribute to native leak channels controlling resting membrane potential, patch-clamp studies were performed to identify biophysical and pharmacological characteristics of macroscopic and unitary K+ currents diagnostic of recombinant TASK channel isoforms. Results indicate K+ conductance (gK+) is mediated almost exclusively by a weakly voltage-dependent (leak) K+ channel closely resembling TASK-3. Leak channels exhibited a unitary conductance approximating that expected for TASK-3 under the recording conditions employed, brief mean open times and a voltage-dependent open probability. Extracellular H+ induced voltage-independent inhibition of gK+, exhibiting an IC50 of 56 nM (pH 7.25) and a Hill coefficient of 0.75. Protons inhibited leak channel open probability (Po) by promoting a long-lived closed state (τ > 500 ms). Extracellular Zn2+ mimicked the effects of H+; inhibition of gK+ exhibited an IC50 of 41 μM with a Hill coefficient of 1.26, inhibiting channel gating by promoting a long-lived closed state. Ruthenium red (5 μM) inhibited gK+ by 75.6% at 0 mV. Extracellular Mg2+ induced voltage-dependent block of gK+, inhibiting unitary current amplitude without affecting mean open time. Bupivacaine induced voltage-dependent block of gK+, exhibiting IC50 values of 116 μM at −100 mV and 28 μM at 40 mV with Hill coefficients of 1 at both potentials. Halothane induced a voltage-independent stimulation of gK+ primarily by decreasing the leak channel closed-state dwell time.
影响因子：
8.8
作者：
Kindler, CH;Yost, CS;Gray, AT
通讯作者：
Gray, AT
DOI：
10.1152/ajpendo.00223.2004
发表时间：
2004-12-01
影响因子：
5.1
作者：
Enyeart, JA;Danthi, SJ;Enyeart, JJ
通讯作者：
Enyeart, JJ
影响因子：
--
作者：
Bayliss, Douglas A;Sirois, Jay E;Talley, Edmund M
通讯作者：
Talley, Edmund M