Identity, expression and functional role of the sodium-activated potassium current in vestibular ganglion afferent neurons

Abstract

Vestibular afferent neurons (VANs) transmit information from the vestibular end organs to the central nuclei. This information is encoded within the firing pattern of these cells and is heavily influenced by the K+ conductances expressed by vestibular neurons. In the present study, we describe the presence of a previously unidentified Na+-activated K+ conductance (KNa) in these cells. We observed that the blocking of Na+ channels by tetrodotoxin (TTX) or the substitution of choline for Na+ in the extracellular solution during voltage clamp pulses resulted in the reduction of a sustained outward current that was dependent on the Na+ current. Furthermore, increases in the intracellular concentration of Na+ that were made by blocking the Na+/K+ ATPase with ouabain increased the amplitude of the outward current, and reduction of the intracellular Cl− concentration reduced the TTX-sensitive outward current. The substitution of Li+ for Na+ in the extracellular solution significantly reduced the amplitude of the outward current in voltage clamp pulses and decreased the afterhyperpolarization (AHP) of the action potentials in current clamp experiments. These electrophysiological results are consistent with the presence of mRNA transcripts for the KNa subunits Slick and Slack in the vestibular ganglia and in the sensory epithelium, which were detected using reverse-transcription polymerase chain reaction (RT-PCR). These results are also consistent with the immunolabeling of Slick and Slack protein in isolated vestibular neurons, in the vestibular ganglion and in the vestibular sensory epithelium. These results indicate that KNa channels are expressed in VANs and in their terminals. Furthermore, these data indicate that these channels may contribute to the firing pattern of vestibular neurons.