Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca(2+) Transients in Cultured Skeletal Muscle Fibers

A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC)—the sequential link between action potentials (AP), intracellular Ca(2+) release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca(2+) transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca(2+) imaging to investigate the temporal properties of AP-induced Ca(2+) transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.). Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca(2+) transients (phasic, biphasic, phasic-delayed, and phasic-slow decay); most control muscle fibers show phasic AP-induced Ca(2+) transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca(2+) transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca(2+) transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.