Asic3

Acid-sensing ion channel 3 (ASIC3) (Amiloride-sensitive cation channel 3) (Dorsal root ASIC) (DRASIC)

Spatial tier: STRICT_EXCLUSIVE · Class: ION_CHANNEL · Top region: ME (Median eminence) · Positive regions: 3/554

43.3Discovery Score
35.5Targetability Score
CEvidence grade C
What this means: Asic3: predicted fine-region profile is strict-exclusive, with 3 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in ME: evidence, prediction, innovation

Gene function
Asic3 encodes ASIC3 (DRASIC), a proton-gated, amiloride-sensitive cation channel of the ENaC/degenerin family that forms trimers with ASIC1/ASIC2. Mild acidification opens a fast desensitising Na+ current plus a sustained window current that depolarises the cell; lactate and arachidonic acid modulate it. ASIC3 is best known as a peripheral sensor of tissue acidosis in pain.
Region function
The median eminence is a circumventricular structure where fenestrated portal capillaries, beta-tanycytes and neurosecretory terminals meet, releasing GnRH, TRH, CRH, GHRH and dopamine into pituitary portal blood and gating blood-borne metabolic signals.
Published in this region
inferred No region-specific literature found. Closest: Wang et al. 2020 (Biophys J) profiled pituitary proton sensors and found Asic1, Asic2 and Asic4, but not Asic3, in anterior pituitary secretory cells, while Ohbuchi et al. 2010 (J Physiol) recorded ASIC currents in hypothalamic supraoptic vasopressin neurons.
Predicted function
Prediction: If present in median eminence tanycytes or neurosecretory terminals, ASIC3 would sense portal-blood pH and lactate, coupling metabolic state to terminal excitability and Ca2+ entry and thus to hormone release into portal blood. Asic3 knockout or APETx2 blockade should blunt acid-, exercise- or hypoxia-evoked hormone surges without changing baseline endocrine tone.
Innovation
★★★★★ 5/5 No published work places ASIC3 in the median eminence despite this being the one brain site continuously exposed to blood pH changes.
Tools
Asic3 knockout mice (Price 2001); blockers APETx2 and amiloride; non-proton agonist GMQ; anti-ASIC3 antibodies; tanycyte access via Rax-CreERT2 and ICV AAV1/AAV5.
References

Direct evidence located at the region

No Allen ISH section could be located at this region's centroid for the recorded experiments.

Direct spatial evidence

MERFISH REGION LOCATOR
ME MERFISH region locator
Real single-cell MERFISH coordinates for the ME (Median eminence) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 69013609, image 68812601 -- target region: ME (Median eminence)
Allen ISH experiment 69013609, image 68812601 -- target region: ME (Median eminence)
DIRECT ALLEN ISH
Allen ISH experiment 69013609, image 68812603 -- target region: ME (Median eminence)
Allen ISH experiment 69013609, image 68812603 -- target region: ME (Median eminence)

Regional expression figure

Asic3 regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

ME
0.362
OV
0.132
MH
0.124
RL
0.115
FC
0.114
ARH
0.111
GPi
0.106
DCO
0.099
PN
0.0989
SAG
0.0977
RR
0.0969
PRNr
0.0962
GRN
0.0954
PPN
0.0949
NLL
0.0947
PRNc
0.0946
RN
0.0941
MRN
0.0935
MDRNv
0.093
LAV
0.0928

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.291
Top-region fraction
0.117
Filter status
PASS

Interpretation limits