P2 receptor-mediated signaling in spherical bushy cells of the mammalian cochlear nucleus.
Purinoreceptors of the P2 family contribute strongly to signaling in the cochlea, but little is known about the effects of purinergic neurotransmission in the central auditory system. Here we examine P2 receptor-mediated signaling in the large spherical bushy cells (SBCs) of Mongolian gerbils around the onset of acoustically evoked signal processing (P9-P14). Brief adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) application evoked inward current, membrane depolarization, and somatic Ca2+ signals. Moreover, ATPgammaS changed the SBCs firing pattern from phasic to tonic, when the application was synchronized with depolarizing current injection. This bursting discharge activity was dependent on [Ca2+]i and Ca2+-dependent protein kinase (PKC) activity and is presumably caused by modulation of low-threshold K+ conductance. Activation of P2Y1 receptors could not evoke these changes per se, thus it was concluded that the involvement of P2X receptors seems to be necessary. Ca2+ imaging data showed that both P2X and P2Y1 receptors mediate Ca2+ signals in SBCs where P2Y1 receptors most likely activate the PLC-IP3 (inositol trisphosphate) pathway and release Ca2+ from internal stores. Immunohistochemical staining confirmed the expression of P2X2 and P2Y1 receptor proteins in SBCs, providing additional evidence for the involvement of both receptors in signal transduction in these neurons. Purinergic signaling might modulate excitability of SBCs and thereby contribute to regulation of synaptic strength. Functionally, the increase in firing rate mediated by P2 receptors could reduce temporal precision of the postsynaptic firing, e.g., phase locking, which has an immediate effect on signal processing related to sound localization. This might provide a mechanism for adaptation to the ambient acoustic environment.
Milenkovic
Ivan
I
Institute of Biology II, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Talstrasse 33, D-04103 Leipzig, Germany. mili@uni-leipzig.de
Rinke
Ilka
I
Witte
Mirko
M
Dietz
Beatrice
B
Rübsamen
Rudolf
R
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D017626:Cochlear Nucleus / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005470:Fluorometry / Q000379:methods; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005849:Gerbillinae; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D004791:Enzyme Inhibitors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D050598:Vesicular Glutamate Transport Protein 1; C049925:fura-2-am; C030812:adenosine 5'-O-(2-thiodiphosphate); C022571:adenosine 5'-O-(3-thiotriphosphate); D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C013411:biocytin; D008239:Lysine; D002118:Calcium; D016257:Fura-2