Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain.
The generation of pacemaker activity in heart and brain is mediated by hyperpolarization-activated cation channels that are directly regulated by cyclic nucleotides. We previously cloned a novel member of the voltage-gated K channel family from mouse brain (mBCNG-1) that contained a carboxy-terminal cyclic nucleotide-binding domain (Santoro et al., 1997) and hence proposed it to be a candidate gene for pacemaker channels. Heterologous expression of mBCNG-1 demonstrates that it does indeed code for a channel with properties indistinguishable from pacemaker channels in brain and similar to those in heart. Three additional mouse genes and two human genes closely related to mBCNG-1 display unique patterns of mRNA expression in different tissues, including brain and heart, demonstrating that these channels constitute a widely expressed gene family.
Santoro
B
B
Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA.
Liu
D T
DT
Yao
H
H
Bartsch
D
D
Kandel
E R
ER
Siegelbaum
S A
SA
Tibbs
G R
GR
D000595:Amino Acid Sequence; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001683:Biological Clocks / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D018076:DNA, Complementary / Q000235:genetics; D004553:Electric Conductivity; D015870:Gene Expression; D006321:Heart / Q000502:physiology; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism; D009865:Oocytes; D010138:Pacemaker, Artificial; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D013045:Species Specificity; D014018:Tissue Distribution; D014981:Xenopus
D054815:Cyclic Nucleotide-Gated Cation Channels; D018076:DNA, Complementary; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D011994:Recombinant Proteins; D002586:Cesium; D001464:Barium; D012964:Sodium; D000242:Cyclic AMP; D011188:Potassium