Gene → protein → cell → circulation
Five ways a molecule reaches the whole body.
A channel converts the cell’s energy state into membrane potential and then into blood pressure within seconds. A kinase cascade converts a cytokine into transcription over hours. An antibody does nothing at all until enough copies of it stand close enough together. A protease cascade amplifies itself on any surface that fails to stop it. Each is traced from the protein to the consequence, and each fails in a different way.
Every control on this page is written into the address bar, for all five modules at once. Copy the link to hand someone this exact configuration.
Metabolic switch to vascular tone selected.
01Channel genotype
02Metabolic state
03Pharmacology
A comparison state, not a prediction of natural history.
Molecule to circulation
SUR2B / Kir6.1- ChannelOpen probability0.03%simulated
- MyocyteMembrane potential-34.1mVsimulated
- VesselArteriolar radius1.00×fitted
- CirculationSystemic resistance1.00×fitted
Against the reference channel: +0 mmHg, +0.00 L/min. simulated
Nucleotide dependence
At a resting energy charge the channel is almost entirely shut. Its influence comes from a very large conductance reserve, not from being open.
Resistance across the metabolic axis
The dashed line is the reference resistance. A loss-of-function channel sits above it and cannot come down — the metabolic vasodilator reserve is gone.
The channel itself
Loading structure from the local cache…
Mechanism and evidence
- Molecular lesion
- The channel opens only when Mg-nucleotides occupy the SUR2B nucleotide-binding domains, so it stays largely shut while the cell is well perfused.
- Systemic consequence
- Normal arteriolar calibre and systemic vascular resistance.
- Evidence level
- reference
What these models cannot establish
- Rate constants are educational estimates chosen to sit inside published ranges and reproduce published timescales. They are not fitted values, and no number here should be read as a measurement.
- Drug controls represent mechanism strength. They are not dose, exposure, receptor occupancy, or predicted clinical response, and selectivity is represented only as a single scaling factor.
- The KATP module collapses every vascular bed into one resistance and omits autoregulation, the endothelium, and the baroreflex. The JAK-STAT module represents one receptor and one STAT species.
- Reversing a phenotype in a model organism is not the same as treating a patient. Glibenclamide corrects the Cantú phenotype in mouse and zebrafish models, but an open-label trial in four adults found no significant change in the cardiac phenotype or leg oedema, and the two commonest alleles are themselves glibenclamide-resistant. The drug axis here reproduces that resistance rather than flattering the therapy.
- The complement module models the alternative pathway in full and accepts a classical drive from the immunoglobulin module, which is how the NMOSD section works. It still has no lectin pathway, no C5a and no anaphylatoxin biology, no coagulation crosstalk and no cellular immunity — so no antibody- dependent cell-mediated cytotoxicity, which can kill an astrocyte without complement at all, and no granulocytes, which are conspicuous in NMOSD lesions. Its rate constants are educational estimates: on-surface complement kinetics vary by orders of magnitude with surface chemistry and are not something this module can source honestly. The NMOSD section additionally does not model the blood-brain barrier, how the antibody reaches the astrocyte, oligodendrocyte injury as a secondary event, or any repair.
- No module here can be used for variant classification, prognosis, or treatment selection.