ATP-gated currents in rat primary auditory neurones in situ arise from a heteromultimetric P2X receptor subunit assembly.
Spiral ganglion neurones provide the primary afferent innervation to sensory hair cells within the mammalian cochlea. Recent evidence suggests that their function may be modulated by purinergic signalling mechanisms, associated with release of adenosine 5'-triphosphate (ATP). Utilising a newly developed slice preparation of the neonatal rat cochlea, we have investigated the response of neurones in situ, to purinergic agonists and antagonists using whole-cell voltage clamp recordings. In cells identified as type I spiral ganglion neurones on the basis of morphology and voltage-dependent conductances, pressure-applied ATP, alpha,beta-methyleneATP (alpha,beta-meATP), 2-methylthioATP (2-MeSATP) and adenosine 5'-diphosphate (ADP) elicited a consistent phenotype of desensitising, inwardly rectifying current. The ATP-activated currents were reversibly blocked by the P2X receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM), and 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP; IC(50) 407 nM). Neurones were more sensitive to ATP at low pH. The EC(50) value for ATP shifted from 18 microM at pH 7.3, to 1 microM at pH 6.3, with Hill coefficients of approximately 1. The results indicate that ATP-gated ion channels in spiral ganglion neurones arise from a specific heteromultimeric assembly of P2X receptor subunits which has no correspondence with present recombinant P2X receptor models.
Salih
S G
SG
Physiology Division, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Jagger
D J
DJ
Housley
G D
GD
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D003056:Cochlear Nerve / Q000187:drug effects* / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D013136:Spiral Ganglion / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate