Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha1D subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their relative contribution to total L-type Ca2+ currents and their physiological role and significance as a drug target remain unknown. Therefore, we generated D-LTCC deficient mice (alpha1D-/-) that were viable with no major disturbances of glucose metabolism. alpha1D-/-mice were deaf due to the complete absence of L-type currents in cochlear inner hair cells and degeneration of outer and inner hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha1D-/- mice. We conclude that alpha1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.

Maintenance of postural balance requires an active sensorimotor control system. Current data are limited and sometimes conflicting regarding the influence of the proprioceptive, visual, and vestibular afferent systems on posture control in children. This study investigated the development of sensory organization according to each sensory component in relation to age and sex. A total of 140 children (70 males, 70 females; mean age 10y [SD 4y]; age range 3y 5mo-16y 2mo) and 20 adults (10 males, 10 females; mean age 30y 6mo [SD 8y 4mo]; age range 17y 2mo-49y 1mo) were examined using the Sensory Organization Test. Participants were tested in three visual conditions (eyes open, blindfolded, and sway-referenced visual enclosure) while standing on either a fixed or a sway-referenced force platform. Mean equilibrium scores for the six balance conditions showed rapid increases and maturation ceiling levels for age-related development of the sensorimotor control system. Proprioceptive function seemed to mature at 3 to 4 years of age. Visual and vestibular afferent systems reached adult level at 15 to 16 years of age, revealing differences between young males and females. Characterizing balance impairments can contribute to the diagnostic evaluation of neuromotor disorders.

Carbon dots were synthesized by a simple and green strategy for selective and sensitive Cu(2+) ion detection using both down and upconversion fluorescence. These fluorescent nanosensors show low cytotoxicity and are applied for intracellular sensing and imaging of Cu(2+) in biological systems.

Deafferentation of the auditory nerve from loss of sensory cells is associated with degeneration of nerve fibers and spiral ganglion neurons (SGN). SGN survival following deafferentation can be enhanced by application of neurotrophic factors (NTF), and NTF can induce the regrowth of SGN peripheral processes. Cochlear prostheses could provide targets for regrowth of afferent peripheral processes, enhancing neural integration of the implant, decreasing stimulation thresholds, and increasing specificity of stimulation. The present study analyzed distribution of afferent and efferent nerve fibers following deafness in guinea pigs using specific markers (parvalbumin for afferents, synaptophysin for efferent fibers) and the effect of brain derived neurotrophic factor (BDNF) in combination with acidic fibroblast growth factor (aFGF). Immediate treatment following deafness was compared with 3-week-delayed NTF treatment. Histology of the cochlea with immunohistochemical techniques allowed quantitative analysis of neuron and axonal changes. Effects of NTF were assessed at the light and electron microscopic levels. Chronic BDNF/aFGF resulted in a significantly increased number of afferent peripheral processes in both immediate- and delayed-treatment groups. Outgrowth of afferent nerve fibers into the scala tympani were observed, and SGN densities were found to be higher than in normal hearing animals. These new SGN might have developed from endogenous progenitor/stem cells, recently reported in human and mouse cochlea, under these experimental conditions of deafferentation-induced stress and NTF treatment. NTF treatment provided no enhanced maintenance of efferent fibers, although some synaptophysin-positive fibers were detected at atypical sites, suggesting some sprouting of efferent fibers.