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Fiber‐Type Effects of K ATP Channel Inhibition via Glibenclamide on the Recovery of Interstitial PO 2 Following Muscle Contractions in Rats
Author(s) -
Schulze Kiana M.,
Colburn Trenton D.,
Weber Ramona E.,
Hageman K. Sue,
Behnke Bradley J.,
Poole David C.,
Musch Timothy I.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06075
Subject(s) - glibenclamide , chemistry , vasodilation , endocrinology , medicine , isometric exercise , potassium channel , biophysics , diabetes mellitus , biology
K ATP channels allow influx of potassium (K + ) which hyperpolarizes cell membranes. Glibenclamide (GLI) is a second‐order sulphonylurea often prescribed to Type II diabetic patients to increase insulin release via the inhibition of pancreatic K ATP channels. Unfortunately, in vivo studies demonstrate that GLI impairs vasodilation and O 2 delivery‐utilization matching (assessed via interstitial PO 2 , PO 2 is ) in contracting skeletal muscle. Determination of GLI’s impact on PO 2 is kinetics (T 63; time taken to reach 63% of the final response) across muscles comprised of different fiber types during post‐exercise recovery may provide novel insights into mechanisms of fatigue in patients prescribed this medication, particularly in repeated bouts of activity. Purpose To test the hypothesis that K ATP channel inhibition via GLI will slow PO 2 is kinetics, thus lengthening recovery time following contractions in rat fast‐(mixed gastrocnemius, MG) and slow‐(soleus, SOL) twitch muscles. Methods In twenty Sprague‐Dawley rats (male (n=5), female (n=8) and ovariectomized female (F‐OVX; n=7)), PO 2 is was determined, before and after GLI superfusion (5 mg kg −1 ), via phosphorescence quenching (G4). Measurements were taken for 3 min throughout the duration of, and 3 min following, the cessation of electrically‐induced contractions (180 s, 1 Hz, 7V). Blood flow was measured via fluorescent‐labeled microspheres in the last 30 seconds of contractions (15 μm). Results In both muscles, PO 2 is recovered to its precontracting level in control and GLI conditions within the 3 min measurement window. However, GLI significantly slowed PO 2 is recovery following contractions in the MG (T 63 : 87.7 ± 4.6 vs 117.4 ± 7.9 s; p < 0.05), but not in the SOL (73.7 ± 8.8 vs 84.8 ± 11.2 s; p > 0.05). The PO 2 is value at which T 63 occurred was not significantly different between the control and GLI conditions for MG or SOL. During contractions, blood flow was attenuated in the MG following GLI (53 ± 4 vs 39 ± 3 ml/100 g/min; p < 0.05), but not in the SOL (37 ± 4 vs 35 ± 5; p > 0.05). Conclusion These data highlight the role of K ATP channel function in supporting PO 2 is recovery of fast‐twitch oxidative fiber types due in part to elevated blood flow. These effects of sulphonylurea medication (i.e. GLI) may explain, in part, the early onset of exhaustion in patients performing high‐intensity exercise and/or activities of daily living that recruit fast‐twitch muscles. Support or Funding Information Supported by NIH Grants: HL108328 (T.I.M and D.C.P) and F31HL145981 (T.D.C)