Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers.

Erick O Hernández-Ochoa,Martin F Schneider,Quinton Banks

doi:10.1155/2017/1509048

Erick O Hernández-Ochoa, Martin F Schneider + Show 1 more

Open Access

https://doi.org/10.1155/2017/1509048

Copy DOI

Abstract

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 Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ 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 Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay); most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ 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.

Highlights

Diabetes mellitus (DM), a complex metabolic syndrome, is due to the inability of the pancreas to produce and/or secrete insulin, referred as insulin deficiency or improper insulin signal transduction by tissues like hepatic, fat, and skeletal muscle, known as insulin resistance
Numerous studies have investigated how changes in skeletal muscle excitability, Ca2+ signaling, and contractility occur in acute and long-term hyperglycemia [12, 13, 20, 21, 47, 48]; few studies have examined the impact of diabetes mellitus on the excitability [22], contractility [49], and Ca2+ signaling [24] of the skeletal muscle at the cellular level
Little is known about the temporal properties of action potentials (AP)-evoked Ca2+ signals during acute hyperglycemia

Summary

Introduction

Diabetes mellitus (DM), a complex metabolic syndrome, is due to the inability of the pancreas to produce and/or secrete insulin, referred as insulin deficiency or improper insulin signal transduction by tissues like hepatic, fat, and skeletal muscle, known as insulin resistance. In either insulin deficiency or resistance, the cells are unable to adequately metabolize the glucose, leading to hyperglycemia, the hallmark of the disease. Late complications of diabetes affect both the quality and quantity of life, resulting in major health costs [1]. The disease progression of both type 1 (T1D) and type 2 (T2D) diabetes are different, yet the clinical manifestations and complications are often similar [1]. Glucose levels reach abnormal elevated values ranging from 120 to 1200 mg/dL [2,3,4]. In addition to the change in glucose concentration, hyperglycemia is accompanied by significant changes in plasma osmolarity [2, 4, 5]

Methods

Results

Conclusion