Cacna1s

Voltage-dependent L-type calcium channel subunit alpha-1S (Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle) (Dihydropyridine receptor) (DHPR) (Voltage-gated calcium channel su

Spatial tier: RESTRICTED · Class: ION_CHANNEL · Top region: PVpo (Periventricular hypothalamic nucleus, preoptic part) · Positive regions: 18/554

45.8Discovery Score
38.0Targetability Score
CEvidence grade C
What this means: Cacna1s: fine CCF profile is restricted toward PVpo (top regions: PVpo, AD, PVT, PVi, SCO; 18 positive regions); direct spatial validation is still required.

Function in PVpo: evidence, prediction, innovation

Gene function
Cacna1s encodes Cav1.1, the pore-forming alpha-1S subunit of the skeletal-muscle L-type calcium channel, also called the dihydropyridine receptor. In muscle it works mostly as a voltage sensor mechanically coupled to the ryanodine receptor RyR1 to trigger calcium release for contraction, rather than as a major calcium conduit. Mutations cause hypokalaemic periodic paralysis and malignant hyperthermia susceptibility.
Region function
The preoptic periventricular hypothalamic nucleus lines the third ventricle and contributes to neuroendocrine control, sleep and thermoregulation.
Published in this region
none No region-specific literature found. Cacna1s is essentially a skeletal-muscle gene (Flucher 2020; Bannister 2013), and neuronal L-type currents in hypothalamus are carried by Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d), so a PVpo signal most plausibly reflects vascular or perivascular tissue, or low-confidence probe signal, rather than genuine neuronal Cav1.1.
Predicted function
Prediction: genuine neuronal Cav1.1 here is unlikely, and the first experiment should be validation by RNAscope or a well-characterised antibody rather than manipulation. If confirmed, the most plausible role is a dihydropyridine-sensitive, slowly inactivating L-type conductance supporting plateau potentials and activity-dependent CREB signalling in periventricular neuroendocrine cells, duplicating functions normally attributed to Cav1.2 and Cav1.3. A conditional preoptic knockout is predicted to produce no thermoregulatory or neuroendocrine phenotype.
Innovation
★★☆☆☆ 2/5 Low, because the most probable explanation for this pairing is a mapping artefact of a skeletal-muscle gene rather than untapped brain biology.
Tools
Cacna1s floxed and muscular dysgenesis (mdg) mice; dihydropyridines nifedipine and nimodipine and the agonist Bay K8644, none subtype-selective; monoclonal anti-Cav1.1 antibodies from muscle work; no Cacna1s-Cre line.
References

Direct evidence located at the region

Cacna1s Allen ISH at the CCF centroid of PVpo

Allen ISH experiment 70723167, section image 70418965 (section 146): the section that contains the CCF centroid of Periventricular hypothalamic nucleus, preoptic part according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Cacna1s Allen ISH at the CCF centroid of PVpo

Allen ISH experiment 71307208, section image 71162497 (section 149): the section that contains the CCF centroid of Periventricular hypothalamic nucleus, preoptic part according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Direct spatial evidence

MERFISH REGION LOCATOR
PVpo MERFISH region locator
Real single-cell MERFISH coordinates for the PVpo (Periventricular hypothalamic nucleus, preoptic part) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

Cacna1s regional expression profile

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

Spatial profile

PVpo
0.6
AD
0.586
PVT
0.563
PVi
0.426
SCO
0.36
IMD
0.329
LSc
0.315
PVa
0.281
LING
0.276
CM
0.231
MD
0.221
OV
0.214
SFO
0.195
AV
0.175
PVH
0.169
CL
0.167
Xi
0.162
AMd
0.161
AMv
0.155
PT
0.148

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.342
Top-region fraction
0.068
Filter status
PASS

Interpretation limits