Biology subjects

Raphael, R. M.

Publications and source records attributed to Raphael, R. M..

3 recordsLinked to original sources

bioRxiv2025

Close Packing of Cells in Vestibular Epithelia Supports Local Electrical Potentials that Reduce Latency of Action Potential Generation

In the vestibular system, upon transduction of head motion, ionic currents from type I sensory hair cells alter [K+] and electrical potentials in an extended synaptic cleft formed by a calyx terminal of the associated afferent neuron. During excitatory stimuli, these changes in turn modulate post-synaptic currents across the calyx inner face to depolarize the afferent and initiate action potentials. Within the tightly packed columnar vestibular sensory epithelium, electrical currents from the hair cell and calyx must also traverse non-synaptic extracellular spaces and generate local extracellular potentials before dispersing into the perilymph beneath the basement membrane. Here we show that such dynamic electrical potentials enhance action potential generation by reducing outward K+ currents on both the inner and outer faces of the calyx. This effect also influences adjacent calyces and may explain the abundance of calyx terminals in amniotes where there is a need for rapid recognition of changes in head orientation and acceleration.

neuroscience↗

bioRxiv2021

A Biophysical Model of Nonquantal Transmission at the Vestibular Hair Cell-Calyx Synapse: KLV currents Modulate Fast Electrical and Slow K+ potentials in the Synaptic Cleft

Vestibular hair cells transmit information about head position and motion across synapses to primary afferent neurons. At some of these synapses, the afferent neuron envelopes the hair cell, forming an enlarged synaptic terminal called a calyx. The vestibular hair cell-calyx synapse supports a mysterious form of electrical transmission that does not involve gap junctions termed nonquantal transmission (NQT). The NQT mechanism is thought to involve the flow of ions from the pre-synaptic hair cell to the post-synaptic calyx through low-voltage-activated channels driven by changes in cleft [K+] as K+ exits the hair cell. However, this hypothesis has not been tested with a quantitative model and the possible role of an electrical potential in the cleft has remained speculative. Here we present a computational model that captures salient experimental observations of NQT and identifies overlooked features that corroborate the existence of an electrical potential ({phi}) in the synaptic cleft. We show that changes in cleft{phi} reduce transmission latency and illustrate the relative contributions of both cleft [K+] and{phi} to the gain and phase of NQT. We further demonstrate that the magnitude and speed of NQT depend on calyx morphology and that increasing calyx height reduces action potential latency in the calyx afferent. These predictions are consistent with the idea that the calyx evolved to enhance NQT and speed up vestibular signals that drive neural circuits controlling gaze, balance, and orientation. Significance StatementThe ability of the vestibular system to drive the fastest reflexes in the nervous system depends on rapid transmission of mechanosensory signals at vestibular hair cell synapses. In mammals and other amniotes, afferent neurons form unusually large calyx terminals on certain hair cells, and communication at these synapses includes nonquantal transmission (NQT), which avoids the synaptic delay of quantal transmission. We present a quantitative model that shows how NQT depends on the extent of the calyx covering the hair cell and attributes the short latency of NQT to changes in synaptic cleft electrical potential caused by current flowing through open potassium channels in the hair cell. This previously undescribed mechanism may act at other synapses.

neuroscience↗

bioRxiv2019

3D Ultrastructure of the Cochlear Outer Hair Cell Lateral Wall Revealed By Electron Tomography

Outer hair cells in the mammalian cochlea display a unique type of voltage-induced mechanical movement, termed electromotility, which amplifies auditory signals and contributes to the sensitivity and frequency selectivity of mammalian hearing. Electromotility occurs in the outer hair cell (OHC) lateral wall, and it is not fully understood how the supramolecular architecture of the lateral wall enables this unique form of cellular motility. Employing electron tomography of high-pressure frozen and freeze-substituted OHCs, we visualized the 3D structure and organization of the membrane and cytoskeletal components of the OHC lateral wall. The subsurface cisterna (SSC) is a highly prominent feature, and we report that the SSC membranes and lumen possess hexagonally ordered arrays of particles that endow the SSC with a previously unrealized anisotropic structural rigidity. We also find the SSC is tightly connected to adjacent actin filaments by short filamentous protein connections spaced at regular intervals. Pillar proteins that join the plasma membrane to the cytoskeleton appear as variable structures considerably thinner than actin filaments and significantly more flexible than actin-SSC links. The structurally rich organization and rigidity of the SSC coupled with apparently weaker mechanical connections between the plasma membrane and cytoskeleton reveal that the membrane-cytoskeletal architecture of the OHC lateral wall is more complex than previously appreciated. These observations are important for our understanding of OHC mechanics and need to be considered in computational models of OHC electromotility that incorporate subcellular features.

biophysics↗