Acid-sensing ion channels in neurones of the rat suprachiasmatic nucleus.
We used reduced slice reparations to study ASIC-like currents in the rat central clock suprachiasmatic nucleus (SCN). In reduced SCN preparations, a drop of extracellular pH evoked a desensitizing inward current to excite SCN neurones to fire at higher rates. Under voltage-clamped conditions, all SCN neurones responded to a 5 s pH step to 6.4 with an inward current that decayed with an average time constant of 1.2 s to 10% of the peak at the end of step. The current was blocked by amiloride with an IC(50) of 14 microm and was carried mainly by Na(+), suggesting an origin of ASIC-like channels. The SCN neurones were sensitive to neutral pH, with 94% of cells responding to pH 7.0 with an inward current. The study of sensitivity to pH between 7.0 and 4.4 revealed a two-component dose-dependent H(+) activation in most SCN neurones, with the first component (85% in amplitude) having a pH(50) of 6.6, and the second (15%) a pH(50) of 5. The ASIC-like currents were potentiated by lactate and low Ca(2+), but were inhibited by Zn(2+). RT-PCR analysis demonstrated the presence of mRNA for ASIC1a, 2a, 2b, and 3 in SCN. Compared to other central neurones, the unique presence of ASIC3 along with ASIC1a in SCN neurones may contribute to the high pH sensitivity and unusual inhibition by Zn(2+). The high pH sensitivity suggests that the SCN neurones are susceptive to extracellular acidification of physiological origins and that the ASIC current might play a role in regulating SCN excitability.
Chen
Chun-Hao
CH
Department of Physiology and Pharmacology, Chang Gung University School of Medicine, Kwei-San, Tao-Yuan, Taiwan.
Hsu
Yi-Ting
YT
Chen
Chih-Cheng
CC
Huang
Rong-Chi
RC
D062565:Acid Sensing Ion Channels; D000143:Acids / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D003627:Data Interpretation, Statistical; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000502:physiology
C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D000143:Acids; D004232:Diuretics; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000584:Amiloride; D012964:Sodium