Loss Of Cellular Control Research Articles

Identification of the Involvement of Potassium Channels in Fibromyalgia

Fibromyalgia is a central sensitivity syndrome that presents with chronic pain, fatigue, cognitive dysfunction, and disordered sleep. The pathophysiology which due to multisensory hypersensitivity of the central nervous system involves neuronal excitability leading to central sensitization. Treatments of the challenges associated with the complexities of fibromyalgia involve combinations of pharmacological and non-pharmacological therapeutic approaches which often offer limited benefit. Potassium (K+) channels play a fundamental role in establishing and maintaining stability of neuronal activity. The large molecular diversity and distribution of K+ channels support involvement in a broad range of physiological functions. In nociceptive pathways, neuronal hyperexcitability leading to pain sensation has been associated with reduced function of K+ channels and loss of cellular control. This article reviews the evidence of involvement of K+ channels in fibromyalgia. A potential role both in the pathophysiological processes responsible for the symptoms of fibromyalgia and as therapeutic targets for the management of the condition is considered.

Regulation of ornithine decarboxylase gene expression in normal and transformed hamster embryo fibroblasts following stimulation by 12-O-tetradecanoylphorbol-13-acetate.

We have compared the regulation of ornithine decarboxylase (ODC) gene expression in primary cultures of hamster embryo fibroblasts and in two independently transformed hamster embryo cell lines. Previous studies have demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) can greatly potentiate the serum growth factor induction of ODC enzyme activity in transformed cells, but not in normal hamster embryo fibroblasts. Treatment of either normal or transformed cells with both TPA and serum yielded greater accumulations of ODC mRNA than with either treatment alone, which is consistent with changes at the protein level. However, treatment of the transformed cells with TPA and serum resulted in a greater increase in steady state levels of ODC mRNA than that observed using normal fibroblasts. The time course for the induction of ODC mRNA was similar for both normal and transformed cells with maximal accumulations 4-8 h after treatment. Studies with actinomycin D further suggests that ODC mRNA is comparatively long-lived in both normal and transformed cells. The accumulation of ODC mRNA after stimulation with TPA and serum is blocked by cycloheximide in normal hamster fibroblasts suggesting that this induction is dependent upon protein synthesis. In contrast, cycloheximide did not affect the accumulation of ODC mRNA under similar treatment conditions in transformed cells. This altered regulation of ODC gene expression in transformed hamster embryo fibroblasts cannot be explained by either gene rearrangement or the amplification of an ODC gene. These data suggest that transformation of hamster embryo cells results in a loss of cellular control over ODC gene regulation which includes an alteration in the requirement for protein synthesis for ODC mRNA accumulation.

Electron microscopic study of bone surface changes during aging. The loss of cellular control and biofeedback.

An electron microscopic study was made to determine (1) the effects of aging on periosteal and endosteal bone surfaces and (2) whether the membrane-like arrangement of osteoblasts at bone surfaces was retained during aging. Short-lived BNL inbred Swiss albino mice 5 to 130 weeks of age were perfused with glutaraldehyde. Femoral samples were taken and fixed in cold glutaraldehyde, decalcified in EDTA, and postfixed in OsO4. Epon sections were cut and stained with uranyl acetate and lead citrate. In young mice, during bone formation a zone of osteoid was observed while the preosseous zone above consisted of young collagen fibers in formation. The osteoblasts formed a tight membrane-like structure at all bone surfaces. Where bone formation did not occur, single and multiple osmiophilic laminae were observed. With increasing age collagen formation became diminished as did the width of the preosseous and osteoid zones. Subsequently, the zones disappeared. Increased surface structural complexity was seen in some areas, while other areas revealed simplification with advancing age. This depended upon the net accretionary or resorptive activity at a given surface. The membrane-like arrangement of osteogenic cells was lost in 104-week-old animals, exposing bone surfaces to physio-chemical changes not under cellular control and biofeedback.