title: In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects.
abstract: 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.
authors.affiliation: Department of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Chofu, Tokyo, Japan; and.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Eshima
authors.affiliation: Departments of Anatomy & Physiology and Kinesiology, Kansas State University, Manhattan, Kansas.
authors.forename: David C
authors.initials: DC
authors.lastname: Poole
authors.affiliation: Department of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Chofu, Tokyo, Japan; and kano@pc.uec.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kano
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D004558:Electric Stimulation; D008297:Male; D055806:Microvessels / Q000378:metabolism* / Q000503:physiopathology; D009119:Muscle Contraction; D018763:Muscle Fatigue; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D010313:Partial Pressure; D017208:Rats, Wistar; D020127:Recovery of Function; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
chemical_list: D002021:Buffers; D010100:Oxygen; D002118:Calcium
keywords: bioimaging; contractile performance; fura 2-AM; oxygen exchange; phosphorescence quenching