Abstract
Glutamate is the neurotransmitter released from hair cells. Its clearance from the synaptic cleft can shape neurotransmission and prevent excitotoxicity. This may be particularly important in the inner ear and in other sensory organs where there is a continually high rate of neurotransmitter release. In the case of most cochlear and type II vestibular hair cells, clearance involves the diffusion of glutamate to supporting cells, where it is taken up by EAAT1 (GLAST), a glutamate transporter. A similar mechanism cannot work in vestibular type I hair cells as the presence of calyx endings separates supporting cells from hair-cell synapses. Because of this arrangement, it has been conjectured that a glutamate transporter must be present in the type I hair cell, the calyx ending, or both. Using whole-cell patch-clamp recordings, we demonstrate that a glutamate-activated anion current, attributable to a high-affinity glutamate transporter and blocked by DL-TBOA, is expressed in type I, but not in type II hair cells. Molecular investigations reveal that EAAT4 and EAAT5, two glutamate transporters that could underlie the anion current, are expressed in both type I and type II hair cells and in calyx endings. EAAT4 has been thought to be expressed almost exclusively in the cerebellum and EAAT5 in the retina. Our results show that these two transporters have a wider distribution in mice. This is the first demonstration of the presence of transporters in hair cells and provides one of the few examples of EAATs in presynaptic elements.
Highlights
IntroductionControl of its concentration in the synaptic cleft shapes postsynaptic currents, ensuring high-fidelity information transfer
When cells were held at a membrane potential of 280 mV with a Cl– equilibrium potential, ECl = 20.5 mV, applications of glutamate in the vicinity of the hair cells induced a slowly developing inward current in type I hair cells (Fig. 1C) with a mean peak amplitude of 239.6613.0 pA (n = 11; range: 219 to 255 pA) for 1 mM glutamate applications and 222.067.4 pA (n = 4; range: 215 to 231 pA) for 100 mM glutamate applications (Fig. 1D)
In hair-cell organs, clearance is usually achieved by the diffusion of synaptically released glutamate to supporting cells, where it binds to EAAT1 and is moved intracellularly
Summary
Control of its concentration in the synaptic cleft shapes postsynaptic currents, ensuring high-fidelity information transfer. This is important in sensory receptors that use a continually high rate of neurotransmitter release to encode incoming stimuli. Released neurotransmitter is cleared from the synaptic cleft by a family of integral membrane proteins, the excitatory amino acid transporters (EAATs). Glutamate transport per se is weak in EAAT4 and EAAT5 because of the slower kinetics of capture and transport, limiting the uptake process [4,7,8,9] The latter two transporters use higher-affinity binding to regulate intercellular neurotransmitter concentration. The outward anion current in EAAT1-3 appears to be small because it is masked by the concurrent inward, stoichiometric current [13]
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