title: Bidirectional interactions between h-channels and Na+-K+ pumps in mesencephalic trigeminal neurons.
abstract: 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 I(p) activated by instantaneous I(h) 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 I(h) itself, attributable to a negative shift of the reversal potential for I(h) 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(+) pumpalpha3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.
authors.affiliation: Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan. kang@dent.osaka-u.ac.jp
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Kang
authors.forename: Takuya
authors.initials: T
authors.lastname: Notomi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014278:Trigeminal Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009712:Nucleotides, Cyclic; D015221:Potassium Channels; D021122:Protein Subunits; D011743:Pyrimidines; C082246:ICI D2788; D002586:Cesium; D010042:Ouabain; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium