Synaptic cleft microenvironment influences potassium permeation and synaptic transmission in hair cells surrounded by calyx afferents in the turtle

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 calcium‐activated potassium conductance, G BK , and a low‐voltage‐activating delayed rectifier, G K(LV) , that activates upon elevation of K + c . Calcium influx that enables quantal transmission also activates I BK , an effect that can be blocked internally by BAPTA, and externally by a Ca V 1.3 antagonist or iberiotoxin. Elevation of K + c or chelation of Ca 2+ c linearizes the G K(LV) steady‐state I–V curve, suggesting that the outward rectification observed for G K(LV) may result largely from a potassium‐sensitive relief of Ca 2+ 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 diffusion‐limited synaptic clefts during ongoing activity. Such accumulation can be demonstrated at large appositions such as the hair cell–calyx 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 potassium‐sensitive 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 calcium‐activated potassium conductance, G BK , that can be blocked by agents that disrupt calcium influx or buffer the elevation of Ca 2+ i , as well as by the specific K Ca 1.1 blocker iberiotoxin. Efflux of K + through G BK can rapidly elevate K + c , which speeds the activation and slows the inactivation and deactivation of a second potassium conductance, G K(LV) . Elevation of K + c or chelation of Ca 2+ c linearizes the G K(LV) steady‐state I–V curve, consistent with a K + ‐dependent relief of Ca 2+ inactivation of G K(LV) . As a result, this potassium‐sensitive hair cell conductance pairs with the potassium‐sensitive hyperpolarization‐activated cyclic nucleotide‐gated channel (HCN) conductance in the afferent and creates resistive coupling at the synaptic cleft.