Nonquantal Transmission at the Vestibular Hair Cell-Calyx Synapse: K_LV Currents Modulate Fast Electrical and Slow K⁺ Potentials in the Synaptic Cleft

Abstract

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 referred to as a calyx. The vestibular hair cell-calyx synapse supports nonquantal transmission (NQT), a neurotransmitter-independent mechanism that is exceptionally fast. The underlying biophysical mechanisms that give rise to NQT are not fully understood. Here we present a computational model of NQT that integrates morphological and electrophysiological data. The model predicts that NQT involves two processes: changes in cleft K+ concentration, as previously recognized, and very fast changes in cleft electrical potential. A significant finding is that changes in cleft electrical potential are faster than changes in [K+] or quantal transmission. The electrical potential mechanism thus provides a basis for the exceptional speed of neurotransmission between type I hair cells and primary neurons and explains experimental observations of fast postsynaptic currents. The [K+] mechanism increases the gain of NQT. Both processes are mediated by current flow through low-voltage-activated K+ (KLV) channels located in both pre-synaptic (hair cell) and post-synaptic (calyx inner face) membranes. The model further demonstrates that the calyx morphology is necessary for NQT; as calyx height is increased, NQT increases in size, speed and efficacy at depolarizing the afferent neuron. We propose that the calyx evolved to enhance NQT and speed up signals that drive vestibular reflexes essential for stabilizing the eyes and neck and maintaining balance during rapid and complex head motions.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 unusual large calyx terminals on certain hair cells, and transmission at those 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.

Vestibular Deficits in Deafness: Clinical Presentation, Animal Modeling, and Treatment Solutions

“…Type II hair cells have a more depolarized membrane potential and a smaller activation range ( 47 , 66 , 67 ). We still have much to learn about how calyceal synapses evolved, but one of the driving forces behind their evolution exclusively within the vestibular system may be the need for faster reflexes in a terrestrial environment ( 29 , 47 , 75 ). Further investigations of the relationships between synaptic features, and the geometric and mechanical properties of the hair bundles are required, to shed light on both phylogenic aspects of evolution and morphometric sets for functional outcomes.…”

Simultaneous Dual Recordings From Vestibular Hair Cells and Their Calyx Afferents Demonstrate Multiple Modes of Transmission at These Specialized Endings

“…Rapid inward transduction current would immediately flow out as potassium through HC channels, with much of the current flowing into the extensive synaptic cleft and a minority flowing into the calyx ( Figure 2B ). Such coupling can be analyzed using either Kirchhoff's current or voltage laws, and the conclusion is the same: there would be relatively small voltage gains or drops of a few mV along the cleft depending on the current direction and the precise resistance ( 97 , 110 ). The impact of this on specific channels facing the cleft is unknown and would greatly depend on their position with respect to the apical gap between HC and calyx.…”

Simultaneous dual recordings from vestibular hair cells and their calyx afferents demonstrate multiple modes of transmission at these specialized endings

“…2B). Such coupling can be analyzed using either Kirchhoff’s current or voltage laws, and the conclusion is the same: there would be relatively small voltage gains or drops of a few mV along the cleft depending on the current direction and the precise resistance (98, 102). The impact of this on specific channels facing the cleft is unknown and would greatly depend on their position with respect to the apical gap between HC and calyx.…”

“…The theoretical analysis (97,98) relied on equivalent circuits of the Type I HC, cleft, and calyx to analyze the problem primarily as ephaptic transmission (99-101) embellished by potassium accumulation. In general, this analysis concluded that the potential drops associated with current flow along the cleft from HC base to apex created only minor differences in the driving force for channels facing the cleft, and as a result were not likely to be a major source of coupling (98), but see (102). The possibility that ion accumulation could have the effect suggested by Chen was also examined experimentally (103).…”