Latch-state evidence by vessel type, caliber, and persistence

Frozen criteriafrozen 2026-09-01 · hash fe5e031b8b8f

Fixed before data collection; any later edit fails the site build. A correction would be a new study superseding this one.

search protocol (re-runnable)

Discovery runs only after this freeze, by the executing agent's own web search plus direct retrieval of primary documents (PubMed and PubMed Central, Crossref DOI resolution, publisher pages); no deep-research assistant is used, and no brief is cited. Literal queries, each run as written: [latch bridge smooth muscle force maintenance energetic cost]; [economy of force maintenance vascular smooth muscle oxygen consumption]; [stress phosphorylation dissociation arterial smooth muscle]; [latch state arteriole resistance vessel]; [skeletal muscle arteriole myosin light chain phosphorylation sustained constriction]; [precapillary sphincter smooth muscle sustained contraction phosphorylation]; [cannulated pressurized arteriole myogenic tone LC20 phosphorylation shortening velocity]; [latch bridge absence saphenous artery]; [tonic versus phasic smooth muscle myosin dephosphorylation force maintenance]; [smooth muscle ATP consumption cross-bridge phosphorylation carotid media]. Citation chaining, forward and backward, from each identified anchor paper: Dillon et al. 1981 (10.1126/science.6893872), Hai & Murphy 1988 (the case's SRC-HAI-MURPHY-1988), Wingard et al. 1994 (10.1113/jphysiol.1994.sp020422), Han et al. 2006 (10.1152/ajpheart.00977.2005), Call et al. 2006 (10.1152/ajpheart.00086.2006), Hammell et al. 2022 (10.1085/jgp.202213117). Author-family searches: Murphy RA, Eddinger TJ, Ratz PH, Speich JE, Lauzon A-M, Paul RJ, Siegman MJ, Butler TM. Every cell is verified against the primary document before it enters the table; searches that return nothing are reported as failed searches (§3.11).

candidates known at freeze time — dispositions pre-committed

Method

One row per experimental preparation, not per paper: a study reporting two vessel types under different conditions supplies two rows, and rows sharing an animal cohort, tissue batch, or dataset carry an independence note (§3.10). Every cell is transcribed from the primary document and cited inline with the standard verification label; nothing is completed from memory or from a secondary account. Each row then receives TWO independent grades, recorded separately and never combined into a single score (§3.13). The latch-evidence grade records how directly the report establishes the phenomenon — contemporaneous energetic measurement, biochemical-mechanical measurement, functional inference from shortening velocity or stiffness alone, molecular reconstitution, or model only. The knot-relevance grade records how close the preparation is to what VASO-C020 requires — a pressurized skeletal-muscle arteriole or smaller resistance microvessel, another resistance vessel, or a large artery, vein, or non-vascular preparation. Keeping the axes apart is the point of the table: a carotid ring study can be strong evidence for the phenotype and weak evidence for the location, and collapsing that into one verdict is how a well-established result in the wrong tissue becomes direct support for a claim about muscle knots. Two columns carry the weight the case's own argument turns on. Caliber is recorded as an actual luminal diameter WITH the transmural pressure at which it was measured, because an isometric ring at nominally zero transmural pressure is a different mechanical object from a cannulated vessel regulating its lumen against 40-100 mmHg. Persistence is recorded as whether the activating stimulus remained present, what happened to force or diameter after it was withdrawn, and over what interval — the distinction between economical maintenance under continuing activation and a state that holds on its own. The table reports what the literature contains and does not adjudicate between papers that disagree; disagreements are recorded as the papers state them. Either outcome publishes.

Findings

• No study located meets all four of the conditions the question sets. Across every row, contemporaneous energetic measurement appears only in large tonic arterial preparations — swine and porcine carotid — and never in an arteriole or any resistance microvessel. The frozen literal queries aimed at microvascular energetics returned nothing, and two further searches run specifically for arteriole-level oxygen consumption or ATP economy also returned nothing. The energetic feasibility argument under VASO-C020 therefore rests entirely on measurements made in conduit arteries at zero transmural pressure.→ ledger record VASO-E019
• The target tissue compartment has nevertheless been examined with the right molecular readout, and what it shows does not look like latch. Three rows are pressurized skeletal-muscle resistance vessels — rat cremaster and gracilis — in which LC20 phosphorylation was measured against diameter. In all three, maintained constriction is accompanied by maintained or rising LC20 phosphorylation rather than by force held while activation falls: phosphorylation rises with pressure (27.7% at 30 mmHg to 39.6% at 120 mmHg), rises monophasically with wall tension, and sits at 40% even at 10 mmHg rising to about 55% at 80 mmHg. One of these papers states the conclusion directly, that spontaneous arteriolar tone 'represents a state of maintained smooth muscle activation that requires increases in [Ca2+]i and myosin light-chain phosphorylation'. None of the three was designed as a latch test and none frames itself as one, so this is a mismatch between the hypothesis and the nearest available evidence rather than a refutation of it.→ ledger record VASO-E020
• Latch behaviour is demonstrably not generic across vascular smooth muscle, and the divergence was never followed downstream. The paired rabbit femoral and saphenous rows show sustained stress at falling calcium in the femoral and a 40% stress loss in its own muscular branch, which the authors attribute to expressed motor proteins that do not support latch-bridge formation. Forward citation chaining from both 2006 papers found no study extending that comparison into arterioles or the microcirculation, so the caliber series that would answer this study's question has never been run — which is the specific gap VASO-R004 is now designed to fill.→ ledger record VASO-E021
• Persistence after stimulus withdrawal is untested at every caliber. In all thirteen vessel-level rows the activating stimulus — KCl, norepinephrine, or intraluminal pressure — remained present for the duration of the measurement, and no row followed force or diameter after it was removed. The only persistence result in the table is the 2022 molecular reconstitution, in which purified smooth-muscle myosin maintains force through LC20 dephosphorylation, longer for tonic than phasic myosin. The published record therefore speaks to economical maintenance under continuing activation, and is silent on the autonomous, input-free persistence that a chronic knot would require.
• Two structural cautions came out of the collection that bear on how the phenotype should be read. The 1993 phorbol-ester row reaches maximal stress with slowly cycling cross-bridges independent of both calcium and LC20 phosphorylation, so the latch phenotype can be produced by a route other than the dephosphorylated-bridge mechanism; and the 1987 temperature row shows the phosphorylation-velocity relationship underwriting the latch reading is itself contingent, shifting with temperature between 37 and 23 degrees C and with stimulus strength. Both are reasons the two grading axes were frozen apart, and both argue against treating any single preparation's economy result as a general property of vascular smooth muscle.

Limitations

• Every row was built from the published abstract. No full text was accessible to this collection: the three decisive skeletal-muscle arteriole papers are not in PubMed Central or Europe PMC open access, and the remainder are behind publisher paywalls. Cells that an abstract does not state are recorded as unstated rather than completed from any other source, which is why temperature, endothelial status and branch order are largely blank. A collection with full-text access would fill those columns and could revise cells, though it is unlikely to change the two grades.
• Three candidates found by the search were excluded by the frozen criteria and are named here so the exclusions are visible rather than silent. Butler, Siegman & Mooers 1986 (Am J Physiol 251:C945-C950) argues from rabbit taenia coli energetics that economical force maintenance reflects a general slowing of cross-bridge cycling rather than a distinct class of latch bridges — directly relevant to the mechanism axis, but gastrointestinal smooth muscle bearing on mechanism generally rather than on vessel-type variation, which is the only ground the frozen criteria admit non-vascular tissue on. Takeya et al. 2008 (Am J Physiol Renal Physiol 294:F1487-F1492) quantifies LC20 phosphorylation in single renal afferent arterioles but reports no force or diameter time course, failing the first inclusion rule. Takeya 2016 (J Smooth Muscle Res 52:45-55) is indexed as a review. A successor study should widen the criteria to admit the first of these.
• One pre-committed known candidate could not be resolved: the canine saphenous-vein report said to infer latch formation from an approximately 11.9 per cent fall in maximum shortening velocity. Searches against PubMed and Crossref did not locate it, and it is recorded here as a failed search rather than dropped. Its absence does not affect any finding, since a vein row would grade low on knot relevance in any case.
• Discovery ran against PubMed, Europe PMC and Crossref. Literature that is not indexed there — older non-indexed journals, book chapters, theses — could contain a demonstration this table misses, and the pre-1970 economy literature is poorly covered by these indexes. The completeness claim is therefore the one the freeze committed to: an evidence map of what the frozen strategy locates, not of everything that exists.
• The two grades on each row are the executing agent's judgment applied to the frozen vocabulary, not a measurement. The knot-relevance axis in particular required a call on the rabbit saphenous artery, graded here as a large-vessel preparation because it is a named conduit artery, even though it is the most downstream vessel in the table and carries the study's most interesting negative result.
• Absence of a demonstration is not a demonstration of absence. Nothing in this table shows that skeletal-muscle arterioles cannot form latch bridges. It shows that nobody has measured the energetic cost of maintained constriction at that caliber, that the studies which did measure activation there found it maintained rather than falling, and that no one has withdrawn the stimulus and watched.