Hemodynamic Homeostasis · §3 · renin ↓ with NaCl, TGF ↑ with NaCl

Sensory transduction: PIEZO1/2 baroreceptor and NKCC2 macula densa

Beneath the controllers sit two concrete molecular transducers. PIEZO1/PIEZO2 mechanically activated channels read arterial-wall stretch and feed the fast baroreflex; the apical Na-K-2Cl cotransporter NKCC2 reads luminal NaCl and feeds the slow RAAS/kidney loop. Afferent firing is a shared-R19 spike train (87 spikes). Identity is cited [L]; the absolute Hz and NaCl scales are open [O].

The regulated variables are read by two transducers, each the entry point of one loop. The baroreceptor PIEZO1/2 mechanosensor fires monotonically with pressure and goes flat under double-knockout; the macula-densa NKCC2 chemosensor drives renin inversely and tubuloglomerular feedback positively with luminal NaCl. Molecular identity is cited [L]; absolute firing rates and NaCl concentrations are open [O].

The loops begin at molecules, not abstractions

A control loop is only as concrete as its sensor, so this package names the molecules that read pressure and volume. Two transducers sit beneath the controllers, each the physical entry point of one loop: a mechanically activated channel for the fast pressure loop, and a salt cotransporter for the slow volume loop. Both convert a physical variable into an afferent spike train on the shared substrate, so the “signal” the loops carry is a real, discrete event train rather than a continuous abstraction.

Baroreceptor — PIEZO1/PIEZO2 mechanosensor (fast loop)

The fast loop’s sensor is a mechanically activated cation channel. PIEZO1 and PIEZO2 in the aortic-arch and carotid-sinus afferents convert arterial-wall stretch into firing, with the rate monotone in the pressure-set stretch and saturating at high pressure (an open-probability sigmoid). In the reproduction the intact transduction curve is monotone and the PIEZO double-knockout curve is flat (no afferent), and the afferent output is a shared-R19 spike train (87 discrete all-or-none events on the vendored substrate).

This matches the cited molecular identity: sensory-neuron double-knockout of PIEZO1/2 abolishes the baroreflex and produces labile hypertension (Zeng et al., Science 2018) [L]. Completeness of the PIEZO account is debated in the literature, which is noted rather than resolved here. The package reproduces the transduction curve shape and the knockout-flat phenotype [V]; the absolute firing rate in Hz is left open [O] and is separately anchored in the calibration chapter.

Macula densa — NKCC2 NaCl chemosensor (slow loop)

The slow loop’s sensor is a furosemide-sensitive cotransporter. The apical Na-K-2Cl transporter NKCC2, in the roughly 15–20 macula-densa cells of the juxtaglomerular apparatus, reads luminal NaCl, which tracks distal delivery and glomerular filtration rate. Luminal NaCl drives two monotone outputs: tubuloglomerular feedback (TGF) increases with NaCl (high NaCl → afferent-arteriole constriction → GFR down), while renin moves inversely (low NaCl → renin up → RAAS up).

SGLT2 inhibition raises delivered NaCl in the model (30 → 48 mM), restoring TGF (0.667 → 0.762) and damping hyperfiltration — a leading account of the renal and cardiovascular benefit of SGLT2 inhibitors [L], and the mechanistic link from this slow-loop sensor to a basin-restoring heart-failure therapy treated later. The transduction directions are reproduced [V]; absolute luminal NaCl and GFR scales are open [O].

Afferent seams cited from the sibling package

Two further afferent systems are referenced rather than duplicated, to keep one source of truth. Carotid-body chemoreceptors (O₂/CO₂/pH) and cardiopulmonary volume receptors are afferent seams owned by the cardiorespiratory sibling package; this package cites them where they enter the map and does not re-derive them, which keeps the pressure loop’s sensory layer focused on the two transducers it owns.