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The Journal of Neuroscience, April 7, 2004, 24(14):3694-3702; doi:10.1523/JNEUROSCI.5641-03.2004
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Cellular/Molecular
Bidirectional Interactions between H-Channels and Na+K+ Pumps in Mesencephalic Trigeminal Neurons
Youngnam Kang,1,3
Takuya Notomi,2
Mitsuru Saito,1
Wei Zhang,1 and
Ryuichi Shigemoto2,3
1Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan, 2Department of Physiological Sciences, School of Life Science, Graduate University for Advanced Studies (Sokendai), and Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan, and 3Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan
The Na+K+ pump current (Ip) and the h-current (Ih) 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 Ih leads to the generation of two types of ouabain-sensitive Ip with temporal profiles similar to those of instantaneous and slow components of Ih, presumably reflecting Na+ transients in a restricted cellular space. Moreover, the Ip activated by instantaneous Ih can facilitate the subsequent activation of slow Ih. 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 Ih 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 3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.
Key words: H-channel; Na+K+ pump; bidirectional interactions; Na+-transient; microdomain; spines; excitability; mesencephalic trigeminal neurons
Received Dec 22, 2003;
revised March 1, 2004;
accepted March 1, 2004.
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