Pannexin's Role in Mediating Skeletal Muscle Active Hyperaemia
Bibliographic record
Abstract
The dynamic metabolic rate of skeletal muscle coupled with the fact that discrete motor units can be recruited within a larger muscle bed necessitates a level of vascular control that allows blood flow to be directed to single muscle fibers. While the locus of blood flow regulation is undetermined, mounting evidence suggests capillaries (CAPS) may play a central role in blood flow coordination. This stems from CAPS close proximity to muscle fibres and, that CAPS can be stimulated by products of contraction to increase their own perfusion, via initiating a vasodilatory signal conducted upstream to its controlling arteriole. This cell‐cell communication is necessary to achieve the coordination needed to distribute blood flow to active skeletal muscle fibres. Gap junction dependent spread of hyperpolarization is prevalent in microvascular cell‐cell signaling, however the archetypal characteristics consistent with hyperpolarization are not always observed during conducted responses elicited by muscle contraction. This may suggest a 2 nd pathway involved in conducted signaling. Pannexin (PANX) channels have been implicated in cell‐cell signaling in other tissues. PANX allow the cellular release of ATP into the interstitial space to activate purinergic receptors on neighboring cells. Activated receptors increase intracellular Ca 2+ leading to PANX‐mediated ATP release and propagation of the signal to adjacent cells. We sought to determine if there was a role of PANX in CAP‐initiated condcuted responses. Using intravital microscopy of the hamster cremaster we stimulated CAPS with 1) vasoactive agents relevant to muscle contraction and 2) muscle contraction itself, while observing changes in diameter of the upstream arteriole associated with the stimulated CAP. 1) Micropipetting vasoactive agents; potassium chloride (KCl; 10 mM; n=7), adenosine (ADO, 10 −4 M; n=9), pinacidil (10 −5 M; n=8), SNAP (nitric oxide donor; 10 −6 M; n=13), and acetylcholine (10 −4 M; n=7) produced an upstream arteriolar dilation. However, when PANX blocker, mefloquine (MEF, 10 −5 M) was applied between the CAP stimulation site and observation site, the conducted responses elicited by KCl and ADO were inhibited by 111% and 67% respectively, while having no effect on the conducted response of other dilators. 2) Conducted responses were elicited by contracting muscle fibres underlying CAPS for 2 min while altering contraction frequency (6, 15 & 60 contractions per minute (CPM)) or stimulus frequency (4, 20 & 40 Hz). While each contraction parameter produced an upstream arteriolar dilation, we found that, in the presence of MEF, conducted responses at low (6CPM, n=15) and intermediate (15CPM; n=15) contraction frequency were unaffected but at high (60CPM; n=15) vasodilation was blunted by 35%. Further, MEF blunted the conducted response at low (4 Hz; n=7) and intermediate (20 Hz; n=7) stimulus frequency by 88% and 73%, respectively but not at high (40 Hz; n=7). These data show CAPS elicit a conducted response involving PANX channel signaling, and that this signal is physiologically relevant during skeletal muscle contraction. Evidence of a 2 nd pathway involved in mediating the conducted response begs the question of why 2 pathways exist when they seem to be mediating the same function. Support or Funding Information NSERC Canada. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".