Functional ligand-gated purinergic receptors (P2X) in rat vestibular ganglion neurons.
The expression of purinergic receptors (P2X) on rat vestibular ganglion neurons (VGNs) was examined using whole-cell patch-clamp recordings. An application of adenosine 5'-triphosphate (ATP; 100microM) evoked inward currents in VGNs at a holding potential of -60mV. The decay time constant of the ATP-evoked currents was 2-4s, which is in between the values for rapidly desensitizing subgroups (P2X1 and P2X3) and slowly desensitizing subgroups (P2X2, P2X4, etc.), suggesting the heterogeneous expression of P2X receptors. A dose-response experiment showed an EC(50) of 11.0microM and a Hill's coefficient of 0.82. Suramin (100microM) reversibly inhibited the ATP-evoked inward currents. Alpha, beta-methylene ATP (100microM), a P2X-specific agonist, also evoked inward currents but less extensively than ATP. An application of adenosine 5'-dihosphate (ADP; 100microM) evoked similar, but much smaller, currents. The current-voltage relationship of the ATP-evoked conductance showed pronounced inward rectification with a reversal potential more positive than 0mV, suggesting non-selective cation conductance. However, the channel was not permeable to a large cation (N-methyl-d-glucamine) and acidification (pH 6.3) had little effect on the ATP-evoked conductance. RT-PCR confirmed the expression of five subtypes (P2X2-P2X6) in VGNs. The physiological role of P2X receptors includes the modulation of excitability at the synapses between hair cells and dendrites and/or trophic support (or also neuromodulation) from supporting cells surrounding the VGNs.
Ito
Ken
K
Department of Otolaryngology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. itoken-tky@umin.ac.jp
Chihara
Yasuhiro
Y
Iwasaki
Shinichi
S
Komuta
Yukari
Y
Sugasawa
Masashi
M
Sahara
Yoshinori
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D017950:Ganglia, Sensory / Q000502:physiology*; D008024:Ligands; D023421:Models, Animal; D009431:Neural Conduction / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D013498:Suramin / Q000494:pharmacology; D014725:Vestibular Nerve / Q000502:physiology*
D008024:Ligands; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate