Acid-sensing ion channels in neurones of the rat suprachiasmatic nucleus

J Physiol. 2009 Apr 15;587(Pt 8):1727-37. doi: 10.1113/jphysiol.2008.166918. Epub 2009 Mar 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels
  • Acids / pharmacology
  • Amiloride / pharmacology
  • Animals
  • Data Interpretation, Statistical
  • Diuretics / pharmacology
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Hydrogen-Ion Concentration
  • Ion Channels / drug effects
  • Male
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium / physiology
  • Sodium Channels / drug effects
  • Sodium Channels / physiology*
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / physiology*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / physiology

Substances

  • ASIC3 protein, rat
  • Acid Sensing Ion Channels
  • Acids
  • Diuretics
  • Ion Channels
  • Nerve Tissue Proteins
  • Sodium Channels
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Amiloride
  • Sodium