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

Eshima H, Poole DC, Kano Y. In vivo Ca buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: Fiber-type specific effects. Am J Physiol Regul Integr Comp Physiol 309: R128–R137, 2015. First published May 6, 2015; doi:10.1152/ajpregu.00044.2015.—In Type 1 diabetes, skeletal muscle resting intracellular Ca concentration ([Ca ]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 ]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 ]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 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 ]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 ]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 ]i remained elevated for the entire recovery period (i.e., 1.23 0.03 at 600 s, P 0.05). The inability of [Ca ]i to return to baseline in EDL DIA was not associated with any reduction of SR Ca -ATPase (SERCA) 1 or SERCA2 protein levels (both increased 30–40%, P 0.05). However, PmvO2 recovery kinetics were markedly slowed in EDL such that mean PmvO2 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 ]i. In contrast, this was not the case for SOL (P 0.05) in that neither [Ca ]i nor PmvO2 were deranged in recovery with DIA. In conclusion, recovery of [Ca ]i homeostasis is impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with reduced PmvO2 pressures.