Key points
In central regions of vestibular semicircular canal epithelia, the [K+] in the synaptic cleft ([K+]c) contributes to setting the hair cell and afferent membrane potentials; the potassium efflux from type I hair cells results from the interdependent gating of three conductances.
Elevation of [K+]c occurs through a calciumâactivated potassium conductance, GBK, and a lowâvoltageâactivating delayed rectifier, GK(LV), that activates upon elevation of [K+]c.
Calcium influx that enables quantal transmission also activates IBK, an effect that can be blocked internally by BAPTA, and externally by a CaV1.3 antagonist or iberiotoxin.
Elevation of [K+]c or chelation of [Ca2+]c linearizes the GK(LV) steadyâstate IâV curve, suggesting that the outward rectification observed for GK(LV) may result largely from a potassiumâsensitive relief of Ca2+ inactivation of the channel pore selectivity filter.
Potassium sensitivity of hair cell and afferent conductances allows three modes of transmission: quantal, ion accumulation and resistive coupling to be multiplexed across the synapse.
Abstract
In the vertebrate nervous system, ions accumulate in diffusionâlimited synaptic clefts during ongoing activity. Such accumulation can be demonstrated at large appositions such as the hair cellâcalyx afferent synapses present in central regions of the turtle vestibular semicircular canal epithelia. Type I hair cells influence discharge rates in their calyx afferents by modulating the potassium concentration in the synaptic cleft, [K+]c, which regulates potassiumâsensitive conductances in both hair cell and afferent. Dual recordings from synaptic pairs have demonstrated that, despite a decreased driving force due to potassium accumulation, hair cell depolarization elicits sustained outward currents in the hair cell, and a maintained inward current in the afferent. We used kinetic and pharmacological dissection of the hair cell conductances to understand the interdependence of channel gating and permeation in the context of such restricted extracellular spaces. Hair cell depolarization leads to calcium influx and activation of a large calciumâactivated potassium conductance, GBK, that can be blocked by agents that disrupt calcium influx or buffer the elevation of [Ca2+]i, as well as by the specific KCa1.1 blocker iberiotoxin. Efflux of K+ through GBK can rapidly elevate [K+]c, which speeds the activation and slows the inactivation and deactivation of a second potassium conductance, GK(LV). Elevation of [K+]c or chelation of [Ca2+]c linearizes the GK(LV) steadyâstate IâV curve, consistent with a K+âdependent relief of Ca2+ inactivation of GK(LV). As a result, this potassiumâsensitive hair cell conductance pairs with the potassiumâsensitive hyperpolarizationâactivated cyclic nucleotideâgated channel (HCN) conductance in the afferent and creates resistive coupling at the synaptic cleft.