Acid-sensing ion channels in rat hypothalamic vasopressin neurons of the supraoptic nucleus.
Body fluid balance requires the release of arginine vasopressin (AVP) from the neurohypophysis. The hypothalamic supraoptic nucleus (SON) is a major site of AVP synthesis, and AVP release is controlled somatodendritically or at the level of nerve terminals by electrical activities of magnocellular neurosecretory cells (MNCs). Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive cationic channels that are activated by extracellular acidification. Although ASICs are widely expressed in the central nervous system, functional ASICs have not been assessed in AVP neurons. ASICs are modulated by lactate (La(-)), which reduces the extracellular calcium ion concentration. We hypothesize that ASICs modify neuronal function through La(-) that is generated during local hypoxia resulting from osmotic stimulation in the SON. In the present study, we used the whole-cell patch-clamp technique to show that acid-induced ASIC current is enhanced by La(-) in isolated rat SON MNCs that express an AVP-enhanced green fluorescent protein (eGFP) transgene. Immunohistochemistry and multi-cell reverse transcriptase-polymerase chain reaction experiments revealed that these neurons express the ASIC1a and ASIC2a subunits. In addition, increased La(-) production was specifically observed in the SON after osmotic stress. These results suggest that interaction between ASICs and La(-) in the SON plays an important role in the regulatory mechanism of body fluid homeostasis.
Ohbuchi
Toyoaki
T
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Sato
Kaori
K
Suzuki
Hideaki
H
Okada
Yasunobu
Y
Dayanithi
Govindan
G
Murphy
David
D
Ueta
Yoichi
Y
D062565:Acid Sensing Ion Channels; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D062626:Degenerin Sodium Channels; D003681:Dehydration / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009997:Osmotic Pressure; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic; D014882:Water-Electrolyte Balance
D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D017673:Sodium Chloride, Dietary; C485184:enhanced green fluorescent protein; D001127:Arginine Vasopressin; D049452:Green Fluorescent Proteins; D019344:Lactic Acid; D002118:Calcium