Research Article: Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

Date Published: December 15, 2014

Publisher: Public Library of Science

Author(s): Jianyang Du, Leah R. Reznikov, Michael J. Welsh, Candice Askwith.


Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed in the nervous system and play an important role in fear learning and memory. The function of ASICs in the pituitary, an endocrine gland that contributes to emotions, is unknown. We sought to investigate which ASIC subunits were present in the pituitary and found mRNA expression for all ASIC isoforms, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. We also observed acid-evoked ASIC-like currents in isolated anterior pituitary cells that were absent in mice lacking ASIC1a. The biophysical properties and the responses to PcTx1, amiloride, Ca2+ and Zn2+ suggested that ASIC currents were mediated predominantly by heteromultimeric channels that contained ASIC1a and ASIC2a or ASIC2b. ASIC currents were also sensitive to FMRFamide (Phe-Met-Arg-Phe amide), suggesting that FMRFamide-like compounds might endogenously regulate pituitary ASICs. To determine whether ASICs might regulate pituitary cell function, we applied low pH and found that it increased the intracellular Ca2+ concentration. These data suggest that ASIC channels are present and functionally active in anterior pituitary cells and may therefore influence their function.

Partial Text

Acid sensing ion channels (ASICs) are members of the epithelial sodium channel/degenerin superfamily that are activated by reduced extracellular pH. To date, six proteins of the ASIC family have been identified (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4). ASICs assemble as homo- or hetero-trimers to form proton-gated, voltage-insensitive, Na+ and Ca2+ permeable channels [1]–[9].

Our RT-PCR analysis of pituitary identified transcripts for six ASIC subunits: ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. The electrophysiological experiments then established that anterior pituitary cells expressed ASIC currents. The following biophysical and pharmacological properties of the acid-induced currents suggested which ASIC subunits might contribute to the H+-gated currents.