Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons.
Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons.
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DOI：
10.1152/jn.00054.2014
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发表时间：
2014-11
影响因子：
2.5
通讯作者：
T. Yunoki;K. Takimoto;Kaori Kita;Y. Funahashi;R. Takahashi;H. Matsuyoshi;S. Naito;N. Yoshimura
中科院分区：
文献类型：
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作者：
T. Yunoki;K. Takimoto;Kaori Kita;Y. Funahashi;R. Takahashi;H. Matsuyoshi;S. Naito;N. Yoshimura
目前对支配躯体和内脏组织的伤害性传入神经元A型瞬时K（+）（KA）电流的电生理差异知之甚少。用异凝集素B4（IB 4）-FITC染色将L 6-S1背根神经节（DRG）神经元分为具有不同染色强度的三个群体：阴性至弱、中等和强荧光信号。所有IB 4强烈染色的细胞是阴性的荧光染料，固蓝（FB），注射到膀胱壁，而一部分的体细胞神经元标记的FB，注射到外部尿道真皮，强烈与IB 4染色。在全细胞膜片钳记录中，Phrixotoxin 2（PaTx 2），一种电压门控K（+）（Kv）4通道阻断剂，在IB 4强染色的细胞中表现出对KA电流的电压非依赖性抑制，但在膀胱神经支配细胞中则没有。该毒素还显示电压非依赖性抑制异源表达的Kv4.1电流，而其抑制Kv4.2和Kv4.3电流是电压依赖性的。Kv4.1和Kv4.2之间S3区羧基部分的四个氨基酸交换转移了这一特征。RT-PCR检测到L 6-S1 DRG中Kv4.1和Kv4.3 mRNA的长亚型，而没有显著的Kv4.2 mRNA。Kv4.1和Kv4.3 mRNA水平在激光捕获，IB 4染色的神经元比在膀胱传入神经元。这些结果表明，PaTx 2的行为不同的通道在Kv 4家族和Kv4.1，可能Kv4.3亚基功能参与KA通道的形成在一个亚群的躯体C-纤维神经元，但不是在内脏C-纤维神经元支配膀胱。
Little is known about electrophysiological differences of A-type transient K(+) (KA) currents in nociceptive afferent neurons that innervate somatic and visceral tissues. Staining with isolectin B4 (IB4)-FITC classifies L6-S1 dorsal root ganglion (DRG) neurons into three populations with distinct staining intensities: negative to weak, moderate, and intense fluorescence signals. All IB4 intensely stained cells are negative for a fluorescent dye, Fast Blue (FB), injected into the bladder wall, whereas a fraction of somatic neurons labeled by FB, injected to the external urethral dermis, is intensely stained with IB4. In whole-cell, patch-clamp recordings, phrixotoxin 2 (PaTx2), a voltage-gated K(+) (Kv)4 channel blocker, exhibits voltage-independent inhibition of the KA current in IB4 intensely stained cells but not the one in bladder-innervating cells. The toxin also shows voltage-independent inhibition of heterologously expressed Kv4.1 current, whereas its inhibition of Kv4.2 and Kv4.3 currents is voltage dependent. The swapping of four amino acids at the carboxyl portion of the S3 region between Kv4.1 and Kv4.2 transfers this characteristic. RT-PCRs detected Kv4.1 and the long isoform of Kv4.3 mRNAs without significant Kv4.2 mRNA in L6-S1 DRGs. Kv4.1 and Kv4.3 mRNA levels were higher in laser-captured, IB4-stained neurons than in bladder afferent neurons. These results indicate that PaTx2 acts differently on channels in the Kv4 family and that Kv4.1 and possibly Kv4.3 subunits functionally participate in the formation of KA channels in a subpopulation of somatic C-fiber neurons but not in visceral C-fiber neurons innervating the bladder.