Bidirectional interactions between H-channels and Na+-K+ pumps in mesencephalic trigeminal neurons
Bidirectional interactions between H-channels and Na+-K+ pumps in mesencephalic trigeminal neurons
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DOI：
10.1523/jneurosci.5641-03.2004
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发表时间：
2004-04-07
影响因子：
5.3
通讯作者：
Shigemoto, R
中科院分区：
文献类型：
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作者：
Kang, YN;Notomi, T;Shigemoto, R
Na(+)-K(+)泵电流(i-p)和流经超极化激活通道(h-通道)的h-电流(i-h)参与产生静息电位。这两股电流被认为是独立产生的。我们在这里展示了中脑三叉神经细胞中Na(+)-K(+)泵和h-通道之间的双向相互作用。I-h的激活导致产生两种哇巴因敏感的i-p，其时间分布类似于i-h的瞬时和慢速分量，推测反映了受限细胞空间中的Na(+)瞬变。此外，瞬时Ih激活的Ip可以促进随后慢Ih的激活。用Li(+)取代细胞外的Na(+)也揭示了这种相反和合作的相互作用，Li(+)通过h-通道，但不像Na(+)离子那样强烈地刺激Na(+)-K(+)泵。这些观察结果表明，相互作用是双向的，并由Na(+)离子介导。同样，在用Li(+)取代细胞外Na(+)后，尽管Ih本身增强，但尾部i-h显著减少，这可能是由于Li(+)离子在细胞内积累导致Ih的反转电位负移所致。这表明存在一个微域，在那里可以发生相互作用。因此，Na(+)-K(+)泵与h-通道之间的双向相互作用可能是由Na(+)微区介导的。与这些发现一致的是，超极化激活和环核苷酸调制的亚单位(HCN1/2)和Na(+)-K(+)泵α3亚型共存于具有大量刺的三叉神经中脑神经元的质膜上。
The Na (+) -K (+) pump current (I-p) and the h-current (I-h) flowing through hyperpolarization-activated channels (h-channels) participate in generating the resting potential. These two currents are thought to be produced independently. We show here bidirectional interactions between Na (+)-K (+) pumps and h-channels in mesencephalic trigeminal neurons. Activation of I-h leads to the generation of two types of ouabain-sensitive I-p with temporal profiles similar to those of instantaneous and slow components of I-h, presumably reflecting Na (+) transients in a restricted cellular space. Moreover, the Ip activated by instantaneous Ih can facilitate the subsequent activation of slow I-h. Such counteractive and cooperative interactions were also disclosed by replacing extracellular Na (+) with Li (+), which is permeant through h-channels but does not stimulate the Na (+) -K (+) pump as strongly as Na (+) ions. These observations indicate that the interactions are bidirectional and mediated by Na (+) ions. Also after substitution of extracellular Na (+) with Li (+), the tail I-h was reduced markedly despite an enhancement of Ih itself, attributable to a negative shift of the reversal potential for Ih presumably caused by intracellular accumulation of Li (+) ions. This suggests the presence of a microdomain where the interactions can take place. Thus, the bidirectional interactions between Na (+) -K (+) pumps and h-channels are likely to be mediated by Na (+) microdomain. Consistent with these findings, hyperpolarization-activated and cyclic nucleotide-modulated subunits (HCN1/2) and the Na (+) -K (+) pump alpha3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.