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.