HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body.
HERG-Like potassium current regulates the resting membrane potential in glomus cells of the rabbit carotid body.
复制标题
HERG 样钾电流调节兔颈动脉体血管球细胞的静息膜电位。
DOI：
10.1152/jn.2000.83.3.1150
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发表时间：
2000
影响因子：
2.5
通讯作者：
Prabhakar,NR
中科院分区：
文献类型：
--
作者：
Overholt,JL;Ficker,E;Yang,T;Shams,H;Bright,GR;Prabhakar,NR
颈动脉体血管球细胞静息膜电位下的特定K+通道的直接证据一直缺乏。人类ether-a-go-go-related基因（HERG）的产物产生内向整流电流，已知其有助于其他神经元细胞中的静息膜电位。本研究的目的是确定颈动脉体球细胞是否表达HERG样K+电流，如果是，以确定是否HERG样电流调节静息膜电位。新鲜分离的兔血管球细胞在全细胞电压钳下表现出缓慢衰减的外向电流，激活20-30 mV的静息膜电位。提高细胞外K+揭示了一个缓慢失活的内向尾电流指示HERG样K+电流。HERG样电流没有发现类似于II型细胞的细胞。HERG样电流被多非利特（DOF）以浓度依赖性方式（IC 50 = 13 ± 4 nM，平均值± SE）和高浓度Ba 2+（1和10 mM）阻断。这种内向尾电流的生物物理学和药理学特征表明，它是由HERG样通道进行的。HERG样电流的稳态激活特性（Vh= −44 ± 2 mV）表明它在血管球细胞的静息膜电位下是活跃的。在整个细胞中，电流钳位的血管球细胞（平均静息膜电位，− 48 ± 4 mV），DOF，而不是四乙基铵，引起静息膜电位的显著（13 mV）去极化偏移。使用荧光成像，DOF增加[Ca 2 +] i在分离的血管球细胞。在离体颈动脉体制备中，DOF以浓度依赖性方式增加颈动脉窦神经的基础感觉放电。这些结果表明，血管球细胞表达HERG样电流，该电流在静息膜电位处活跃并负责控制静息膜电位。
Direct evidence for a specific K+channel underlying the resting membrane potential in glomus cells of the carotid body has been absent. The product of the human ether-a-go-go–related gene (HERG) produces inward rectifier currents that are known to contribute to the resting membrane potential in other neuronal cells. The goal of the present study was to determine whether carotid body glomus cells express HERG-like K+current, and if so, to determine whether a HERG-like current regulates the resting membrane potential. Freshly dissociated rabbit glomus cells under whole cell voltage clamp exhibited slowly decaying outward currents that activated 20–30 mV positive to the resting membrane potential. Raising extracellular K+revealed a slowly deactivating inward tail current indicative of HERG-like K+current. HERG-like currents were not found in cells resembling type II cells. The HERG-like current was blocked by dofetilide (DOF) in a concentration-dependent manner (IC50= 13 ± 4 nM, mean ± SE) and high concentrations of Ba2+(1 and 10 mM). The biophysical and pharmacological characteristics of this inward tail current suggest that it is conducted by a HERG-like channel. The steady-state activation properties of the HERG-like current (Vh= −44 ± 2 mV) suggest that it is active at the resting membrane potential in glomus cells. In whole cell, current-clamped glomus cells (average resting membrane potential, − 48 ± 4 mV), DOF, but not tetraethylammonium, caused a significant (13 mV) depolarizing shift in the resting membrane potential. Using fluorescence imaging, DOF increased [Ca2+]iin isolated glomus cells. In an in-vitro carotid body preparation, DOF increased basal sensory discharge in the carotid sinus nerve in a concentration-dependent manner. These results demonstrate that glomus cells express a HERG-like current that is active at, and responsible for controlling the resting membrane potential.