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Dystrophinopathy is caused by mutations in the dystrophin gene at Xp21. Although manifesting carriers of dystrophinopathy have been documented in adults, symptomatic dystrophinopathy in female children is rare. We report on a 13-year-old girl with initial presentation of myalgia at age 7 years and an incidental finding of increased transaminases and creatine kinase at regular health check at age 12 years. At age 13 years, manual muscle testing revealed asymmetric bilateral proximal weakness of extremities. Slight calf hypertrophy and winged scapulae were found. Muscle biopsy revealed a mosaic pattern in dystrophin immunostaining. Mutation analysis of the dystrophin gene revealed a novel de novo c.1150-2delA mutation. Accordingly, the patient was found to be an isolated dystrophinopathy carrier, manifesting limb-girdle pattern of muscle weakness in her childhood. This report suggests that dystrophinopathy should always be considered in female patients with sporadic myopathy. Dystrophin immunostaining and mutation analysis for the dystrophin gene are necessary for final diagnosis, subsequent genetic counseling, and long-term care., (Copyright © 2012. Published by Elsevier B.V.)

Aims: The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC)., Main Methods: Nerve-stimulated muscle contractions and end-plate potentials were performed in mouse phrenic nerve-diaphragm preparations. Acetylcholine (ACh)-induced muscle contractions were performed in the chick biventer cervicis preparations. Presynaptic nerve terminal waveform recordings were performed in mouse triangularis sterni preparations., Key Findings: Amongst the suramin analogues in this study, only the NF449 and suramin were able to reverse the blockade effect produced by d-TC on nerve-stimulated muscle contractions. Each of these suramin analogues (NF007, NF023, NF279 and NF449) alone has no significant effect on the amplitude of nerve-stimulated muscle contractions. NF449 and suramin also showed the antagonising effects on the inhibition of end-plate potentials induced by d-TC. Furthermore, pre-treatment with NF449 can antagonise the inhibition of d-TC in ACh-induced contractions of chick biventer cervicis muscle. NF449 produced a greater rightward shift of the dose-response inhibition curve for d-TC than did suramin. Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors., Significance: These data suggest that NF449 was able to compete with the binding of d-TC on the nicotinic ACh receptors, and the effect of NF449 was more potent than suramin in reducing the inhibition of d-TC. The structure of NF449 may provide useful information for designing potent antidotes against neuromuscular toxins., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The effect of ionomycin on the human KCNQ4 channels expressed in Xenopus leavis oocytes was investigated. KCNQ4 channels expressed in Xenopus oocytes were measured using two-electrode voltage clamp. The activation of KCNQ4 current had slow activation kinetics and low threshold (approximately -50 mV). The expressed current of KCNQ4 showed the half-maximal activation (V(1/2)) was -17.8 mV and blocked almost completely by KCNQ4 channel blockers, linopirdine (300 microM) or bepridil (200 microM). The significant increase of KCNQ4 outward current induced by ionomycin (calcium salt) is about 1.7-fold of control current amplitude at +60 mV and shifted V(1/2) by approximately -8 mV (from -17.8 to -26.0 mV). This effect of ionomycin could be reversed by the further addition of BAPTA-AM (0.3 mM), a membrane-permeable calcium chelator. Furthermore, the increased effect of ionomycin on KCNQ4 current is abolished by pretreatment of linopirdine or bepridil. In contrast, direct cytoplasmic injection of calcium medium (up to 1 mM calcium, 50 nl) did not mimic the effect of ionomycin. In conclusion, the effect of ionomycin on enhancement of KCNQ4 current is independent of intracellular calcium mobilization and possibly acts on intramembrane hydrophobic site of KCNQ4 protein expressed in Xenopus oocytes.

Multiple types of connexin (Cxs) products, including Cx26, Cx30, Cx31, and Cx43, are found by immunolabeling in the mature cochlea. The transcript of Cx29, a newly discovered member of Cx gene family, was also discovered in the cochlea by cDNA macroarray hybridization. However, the functional roles of Cx29 in the cochlea remain unclear. To elucidate whether the Cx29 gap junction protein epsilon 1, GJE1, is localized in the adult mouse and rat cochlea, we performed an immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) analysis. GJE1 was detected in the cochlea neurons, spiral limbus, spiral ligament, organ of Corti, and stria vascularis using IHC analysis. We also show that Cx29 mRNA is present in spiral limbus, spiral ligament, organ of Corti, stria vascularis, and lateral wall by the method of RT-PCR. Higher levels of Cx29 mRNA were found in spiral ligament and spiral limbus, whereas lower level in lateral wall. Our data first provide a comprehensive and detailed pattern of Cx29 gene expression in the mouse and rat cochlea. Knowledge of spatial distribution of Cx29 also allows the identification of candidate genes for deafness and provides important insight into mechanisms that lead to deafness due to mutations in Cx29 gene.