In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2015-07, Vol.309 (2), p.R128-R137
• Main Authors: Eshima, Hiroaki, Poole, David C, Kano, Yutaka
• Format: Article
• Language: English
• Subjects: Animals; Buffers; Calcium - metabolism; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Electric Stimulation; Male; Microvessels - metabolism; Microvessels - physiopathology; Muscle Contraction; Muscle Fatigue; Muscle Fibers, Fast-Twitch - metabolism; Muscle Fibers, Slow-Twitch - metabolism; Muscle, Skeletal - blood supply; Muscle, Skeletal - metabolism; Oxygen - blood; Oxygen Consumption; Partial Pressure; Rats, Wistar; Recovery of Function; Sarcoplasmic Reticulum - metabolism; Time Factors
• ISSN: 1522-1490
• DOI: 10.1152/ajpregu.00044.2015

In Type 1 diabetes, skeletal muscle resting intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis is impaired following muscle contractions. It is unclear to what degree this behavior is contingent upon fiber type and muscle oxygenation conditions. We tested the hypotheses that: 1) the rise in resting [Ca(2+)]i evident in diabetic rat slow-twitch (type I) muscle would be exacerbated in fast-twitch (type II) muscle following contraction; and 2) these elevated [Ca(2+)]i levels would relate to derangement of microvascular partial pressure of oxygen (PmvO2 ) rather than sarcoplasmic reticulum dysfunction per se. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (CONT) groups. Four weeks later extensor digitorum longus (EDL, predominately type II fibers) and soleus (SOL, predominately type I fibers) muscle contractions were elicited by continuous electrical stimulation (120 s, 100 Hz). Ca(2+) imaging was achieved using fura 2-AM in vivo (i.e., circulation intact). DIA increased fatigability in EDL (P < 0.05) but not SOL. In recovery, SOL [Ca(2+)]i either returned to its resting baseline within 150 s (CONT 1.00 ± 0.02 at 600 s) or was not elevated in recovery at all (DIA 1.03 ± 0.02 at 600 s, P > 0.05). In recovery, EDL CONT [Ca(2+)]i also decreased to values not different from baseline (1.06 ± 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA [Ca(2+)]i remained elevated for the entire recovery period (i.e., 1.23 ± 0.03 at 600 s, P < 0.05). The inability of [Ca(2+)]i to return to baseline in EDL DIA was not associated with any reduction of SR Ca(2+)-ATPase (SERCA) 1 or SERCA2 protein levels (both increased 30-40%, P < 0.05). However, Pmv(O2) recovery kinetics were markedly slowed in EDL such that mean Pmv(O2) was substantially depressed (CONT 27.9 ± 2.0 vs. DIA 18.4 ± 2.0 Torr, P < 0.05), and this behavior was associated with the elevated [Ca(2+)]i. In contrast, this was not the case for SOL (P > 0.05) in that neither [Ca(2+)]i nor Pmv(O2) were deranged in recovery with DIA. In conclusion, recovery of [Ca(2+)]i homeostasis is impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with reduced Pmv(O2) pressures.