Comparison of morphology and physiology of two plurisegmental sound-activated interneurones in a bushcricket

The unusual morphology of a sound-activated plurisegmental ascending interneurone (AN5-AG7) in an insect (Ancistrura nigrovittata, Ensifera, Phaneropteridae) is described. This neurone's soma is located in the penultimate abdominal ganglion. The most prominent arborisations with smooth endings are found in the prothoracic ganglion. The neurone terminates with numerous beaded endings in the brain (protocerebrum). All abdominal ganglia including the penultimate contain only tiny side branches of beaded appearance. The neurone's morphology is compared to the morphology of a `typical' sound-activated plurisegmental neurone of bushcrickets with its soma in the prothorax. In the prothoracic ganglion and in the brain the arborisations of the two cells are very similar. Graded potentials and action potentials are generated in the prothoracic portion of both neurones. Both receive excitation mainly by ultrasound, and inhibition by soma-ipsilateral stimuli. Neither wind, substrate vibration nor touch of the abdomen evoke responses in AN5-AG7. It is assumed that early in evolution this neurone had its dendrites in the ganglion which houses the cell body (like cercal interneurones of this neuromere). Profound evolutionary changes probably have taken place to bring about this neuron's modern morphology. Accepted: 12 June 1999     

血脂及血液流变学指标与突发性聋患者听力曲线类型的关系及其临床疗效的影响因素分析

摘要 目的：探究血脂及血液流变学指标与突发性聋（SSHL）患者听力曲线类型的关系,并分析临床疗效的影响因素。方法：选取2020年6月-2022年1月我院收治的103例SSHL患者设为SSHL组,另选取103例体检健康者设为健康组,分析两组血脂水平及血液流变学指标,比较不同听力曲线类型的SSHL患者血脂水平及血液流变学指标,Spearman相关分析血脂水平及血液流变学指标与SSHL患者听力曲线类型的关系,单因素和多因素Logistic回归模型分析SSHL患者临床疗效的影响因素。结果：与健康组比较,SSHL组总胆固醇（TC）、三酰甘油（TG）与全血高切、中切、低切粘度及血浆粘度明显增高（P＜0.05）,高密度脂蛋白-C（HDL-C）、低密度脂蛋白-C（LDL-C）差异比较无统计学意义（P＞0.05）。不同听力曲线类型的SSHL患者各项血脂指标比较差异均无统计学意义（P＞0.05）,不同听力曲线类型的SSHL患者各项血液流变学指标比较差异均有统计学意义（P＜0.05）,其中全聋型患者各项血液流变学指标显著高于低频下降型患者（P＜0.05）。血脂四项与SSHL听力曲线类型无显著相关性（P＞0.05）,而血液流变学指标与SSHL听力曲线类型显著相关（P<0.05）。治疗无效组患者双耳患病比例、听力曲线类型为全聋型比例、全血高切粘度、全血低切粘度、血浆粘度显著高于有效组患者（P＜0.05）,多因素Logistic分析结果显示：双耳患病、听力曲线类型为全聋型、血浆粘度增加为SSHL患者治疗无效的危险因素（P＜0.05）。结论：SSHL患者存在血脂及血液流变学异常,血液流变学与SSHL患者听力曲线类型和临床疗效有一定关系,其中双耳患病、全聋型、血浆粘度增加为SSHL患者治疗无效的危险因素,检测血脂和血液流变学对于SSHL诊治具有一定临床指导意义。     

The role of aquaporins in hearing function and dysfunction

The inner ear is composed by tiny and complex structures that, together with peripheral and central auditory pathways, are responsible for hearing processing. However, not only the anatomy of the cochlea, its compartments and related structures are complex. The mechanisms involved in the regulation of homeostasis in the inner ear fluid, which determines the ionic gradient necessary for hearing and balancing sensory excitability, is an intricate phenomenon that involves several molecules. Among them, Aquaporins (AQP) play a significant role in this process. AQP are part of a family of small, integral membrane proteins that regulate different processes, including bidirectional water and ionic flow in the inner ear. Changes in the expression of these proteins are essential to auditory physiology and several pathophysiological processes in the inner ear. This review focuses on the role of AQP in health and disease of the auditory system.     

Constitutive Gαi Coupling Activity of Very Large G Protein-coupled Receptor 1 (VLGR1) and Its Regulation by PDZD7 Protein

The very large G protein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 β-subunit constitutively inhibited adenylate cyclase (AC) activity through Gα_i coupling. Co-expression of the Gα_iq chimera with the VLGR1 β-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gα_i protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gα_i coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 β-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independent Gα_i signaling pathway of the VLGR1 β-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome.     

Resultant Pressure Distribution Pattern along the Basilar Membrane in the Spiral Shaped Cochlea

The cochlea is an important auditory organ in the inner ear. In most mammals, it is coiled as a spiral. Whether this specific shape influences hearing is still an open problem. By employing a three-dimensional fluid model of the cochlea with an idealized geometry, the influence of the spiral geometry of the cochlea is examined. We obtain solutions of the model through a conformal transformation in a long-wave approximation. Our results show that the net pressure acting on the basilar membrane is not uniform along its spanwise direction. Also, it is shown that the location of the maximum of the spanwise pressure difference in the axial direction has a mode dependence. In the simplest pattern, the present result is consistent with the previous theory based on the Wentzel–Kramers–Brillouin-like approximation (Manoussaki et al., Phys Rev Lett 96:088701, 2006). In this mode, the pressure difference in the spanwise direction is a monotonic function of the distance from the apex and the normal velocity across the channel width is zero. Thus, in the lowest-order approximation, we can neglect the existence of the Reissner’s membrane in the upper channel. However, higher responsive modes show different behavior and, thus, the real maximum is expected to be located not exactly at the apex but at a position determined by the spiral geometry of the cochlea and the width of the cochlear duct. In these modes, the spanwise normal velocities are not zero. Thus, it indicates that one should take into account the detailed geometry of the cochlear duct for a more quantitative result. The present result clearly demonstrates that the spiral geometry and the geometry of the cochlear duct play decisive roles in distributing the wave energy.     

Can spectral cues contribute to species separation in closely related grasshoppers?

 The acridid grasshoppers Chorthippus biguttulus and Ch. mollis, which are closely related and often sympatric species, were compared intra- and interspecifically with regard to the spectra of their calling and courtship songs and of the sound-induced vibrations of the tympanal membrane, as well as the threshold curves of the tympanal nerve. In the low-frequency range but not in the ultrasound region, the maxima of these various curves fall at distinctly different frequencies in the two species. It is shown that the low-frequency sensitivity of the auditory system in both species, especially in females, is well matched to the conspecific song spectra but not to those of the heterospecific songs. Whether these characteristics actually contribute to species discrimination remains to be determined by behavioural tests. Accepted: 23 August 1996     

Altered Inhibition of Cx26 Hemichannels by pH and Zn2+ in the A40V Mutation Associated with Keratitis-Ichthyosis-Deafness Syndrome

Excessive opening of undocked Cx26 hemichannels in the plasma membrane is associated with disease pathogenesis in keratitis-ichthyosis-deafness (KID) syndrome. Thus far, excessive opening of KID mutant hemichannels has been attributed, almost solely, to aberrant inhibition by extracellular Ca²⁺. This study presents two new possible contributing factors, pH and Zn²⁺. Plasma pH levels and micromolar concentrations of Zn²⁺ inhibit WT Cx26 hemichannels. However, A40V KID mutant hemichannels show substantially reduced inhibition by these factors. Using excised patches, acidification was shown to be effective from either side of the membrane, suggesting a protonation site accessible to H⁺ flux through the pore. Sensitivity to pH was not dependent on extracellular aminosulfonate pH buffers. Single channel recordings showed that acidification did not affect unitary conductance or block the hemichannel but rather promoted gating to the closed state with transitions characteristic of the intrinsic loop gating mechanism. Examination of two nearby KID mutants in the E1 domain, G45E and D50N, showed no changes in modulation by pH or Zn²⁺. N-bromo-succinimide, but not thiol-specific reagents, attenuated both pH and Zn²⁺ responses. Individually mutating each of the five His residues in WT Cx26 did not reveal a key His residue that conferred sensitivity to pH or Zn²⁺. From these data and the crystal structure of Cx26 that suggests that Ala-40 contributes to an intrasubunit hydrophobic core, the principal effect of the A40V mutation is probably a perturbation in structure that affects loop gating, thereby affecting multiple factors that act to close Cx26 hemichannels via this gating mechanism.     

Functional Significance of K+ Channel β-Subunit KCNE3 in Auditory Neurons

The KCNE3 β-subunit interacts with and regulates the voltage-dependent gating, kinetics, and pharmacology of a variety of Kv channels in neurons. Because a single neuron may express multiple KCNE3 partners, it is impossible to predict the overall functional relevance of the single transmembrane domain peptide on the pore-forming K⁺ channel subunits with which it associates. In the inner ear, the role of KCNE3 is undefined, despite its association with Meniere disease and tinnitus. To gain insights on the functional significance of KCNE3 in auditory neurons, we examined the properties of spiral ganglion neurons (SGNs) in Kcne3 null mutant neurons relative to their age-matched controls. We demonstrate that null deletion of Kcne3 abolishes characteristic wide variations in the resting membrane potentials of SGNs and yields age-dependent alterations in action potential and firing properties of neurons along the contour of the cochlear axis, in comparison with age-matched wild-type neurons. The properties of basal SGNs were markedly altered in Kcne3^−/− mice compared with the wild-type controls; these include reduced action potential latency, amplitude, and increased firing frequency. Analyses of the underlying conductance demonstrate that null mutation of Kcne3 results in enhanced outward K⁺ currents, which is sufficient to explain the ensuing membrane potential changes. Additionally, we have demonstrated that KCNE3 may regulate the activity of Kv4.2 channels in SGNs. Finally, there were developmentally mediated compensatory changes that occurred such that, by 8 weeks after birth, the electrical properties of the null mutant neurons were virtually indistinguishable from the wild-type neurons, suggesting that ion channel remodeling in auditory neurons progresses beyond hearing onset.