RBP2 stabilizes slow Cav1.3 Ca channel inactivation properties of cochlear inner hair cells.

Cav1.3 L-type Ca channels (LTCCs) in cochlear inner hair cells (IHCs) are essential for hearing as they convert sound-induced graded receptor potentials into tonic postsynaptic glutamate release. To enable fast and indefatigable presynaptic Ca signaling, IHC Cav1.

Deletion of the Ca Channel Subunit αδ3 Differentially Affects Ca2.1 and Ca2.2 Currents in Cultured Spiral Ganglion Neurons Before and After the Onset of Hearing.

Voltage-gated Ca channels are composed of a pore-forming α subunit and auxiliary β and αδ subunits, which modulate Ca current properties and channel trafficking. So far, the partial redundancy and specificity of α for αδ subunits in the CNS have remained largely elusive. Mature spiral ganglion (SG) neurons express αδ subunit isoforms 1, 2, and 3 and multiple Ca channel subtypes.

Cochlea-Specific Deletion of Ca1.3 Calcium Channels Arrests Inner Hair Cell Differentiation and Unravels Pitfalls of Conditional Mouse Models.

Inner hair cell (IHC) Ca1.3 Ca channels are multifunctional channels mediating Ca influx for exocytosis at ribbon synapses, the generation of Ca action potentials in pre-hearing IHCs and gene expression. IHCs of deaf systemic Ca1.

Synaptic coupling of inner ear sensory cells is controlled by brevican-based extracellular matrix baskets resembling perineuronal nets.

Background: Perineuronal nets (PNNs) are specialized aggregations of extracellular matrix (ECM) molecules surrounding specific neurons in the central nervous system (CNS). PNNs are supposed to control synaptic transmission and are frequently associated with neurons firing at high rates, including principal neurons of auditory brainstem nuclei. The origin of high-frequency activity of auditory brainstem neurons is the indefatigable sound-driven transmitter release of inner hair cells (IHCs) in the cochlea.

Fast Ca Transients of Inner Hair Cells Arise Coupled and Uncoupled to Ca Waves of Inner Supporting Cells in the Developing Mouse Cochlea.

Before the onset of hearing, which occurs around postnatal day 12 (P12) in mice, inner hair cells (IHCs) of the immature cochlea generate sound-independent Ca action potentials (APs), which stimulate the auditory pathway and guide maturation of neuronal circuits. During these early postnatal days, intercellular propagating Ca waves elicited by ATP-induced ATP release are found in inner supporting cells (ISCs). It is debated whether IHCs are able to fire Ca APs independently or require a trigger by an ISC Ca wave.

α2δ2 Controls the Function and Trans-Synaptic Coupling of Cav1.3 Channels in Mouse Inner Hair Cells and Is Essential for Normal Hearing.

Unlabelled: The auxiliary subunit αδ2 modulates the abundance and function of voltage-gated calcium channels. Here we show that αδ2 mRNA is expressed in neonatal and mature hair cells. A functional αδ2-null mouse, the ducky mouse (du), showed elevated auditory brainstem response click and frequency-dependent hearing thresholds.

Integrated primary care in Germany: the road ahead.

Problem Statement: Health care delivery in Germany is highly fragmented, resulting in poor vertical and horizontal integration and a system that is focused on curing acute illness or single diseases instead of managing patients with more complex or chronic conditions, or managing the health of determined populations. While it is now widely accepted that a strong primary care system can help improve coordination and responsiveness in health care, primary care has so far not played this role in the German system. Primary care physicians traditionally do not have a gatekeeper function; patients can freely choose and directly access both primary and secondary care providers, making coordination and cooperation within and across sectors difficult.

Drugs, sex, money and power: an HPV vaccine case study.

In this paper we compare the experiences of seven industrialized countries in considering approval and introduction of the world's first cervical cancer-preventing vaccine. Based on case studies, articles from public agencies, professional journals and newspapers we analyse the public debate about the vaccine, examine positions of stakeholder groups and their influence on the course and outcome of this policy process. The analysis shows that the countries considered here approved the vaccine and established related immunization programs exceptionally quickly even though there still exist many uncertainties as to the vaccine's long-term effectiveness, cost-effectiveness and safety.