L-type calcium channels in the auditory system

Abstract The voltage-activated L-type calcium channels Cav1.2 and Cav1.3 mediate Ca2+ influx into neurons at the soma or at dendrites, whereas they are not observed at the presynapse. Surprisingly, in the inner ear, Cav1.3 is indispensable for signal transmission from the presynaptic cochlear inner hair cells to the postsynaptic auditory nerve fibers. Due to Cav1.3 channel clustering at ribbons, i.e., specific presynaptic structures of the hair cells, they promote Ca2+ influx, which triggers calcium-dependent fusion of synaptic vesicles with the plasma membrane. Mutations in Cacna1d, a gene that encodes Cav1.3, result in deafness because release of the neurotransmitter glutamate at the synapses is abolished. Moreover, studies of the auditory pathway have revealed that Cav1.3 plays an important part in the central auditory system as well. Absence of the channel results in severe changes in auditory pathway cytoarchitecture and in abnormal electrophysiological performance of auditory neurons. Furthermore, developmental refinement of tonotopic inhibitory projections in sound localization circuits is disrupted. These aberrations are associated with abnormal sound processing in the auditory pathway. This goes to show that the Cav1.3 channel is essential for inner ear functioning as well as auditory pathway development and performance. Cacna1d therefore represents a prototypal deafness-associated gene, in which mutations result in both peripheral and central aud...
Source: e-Neuroforum - Category: Neuroscience Source Type: research