title: Nonselective cation conductance activated by muscarinic and purinergic receptors in rat spiral ganglion neurons.
abstract: The present study characterizes the ionic conductances activated by acetylcholine (ACh) and ATP, two candidate neuromodulators, in isolated spiral ganglion neurons (SGNs). Brief application (1 s) of ACh evoked in a dose-dependent manner (EC(50) = 4.1 microM) a reversible inward current with a long latency (average 1.3 s), at holding potential (V(h)) = -50 mV. This current was reversibly blocked by atropine and mimicked by muscarine. Application of ATP also evoked a reversible inward current at V(h) = -50 mV, but the current showed two components. A fast component with a short latency was largely reduced when N-methyl-D-glucamine (NMDG) replaced extracellular sodium, implying a P2X-like ionotropic conductance. The second component had a longer latency (average 1.1 s) and was presumably activated by metabotropic P2Y-like receptors. The second component of ATP-evoked current shared similar characteristics with the responses evoked by ACh: the current reversed near 0 mV, displayed inward rectification, could be carried by NMDG, and was insensitive to extracellular and intracellular calcium. This ACh-/ATP-evoked conductance was reversibly inhibited by preapplication of ionomycin. These results suggest that muscarinic receptors and purinergic metabotropic receptors activate a similar large nonselective cation conductance via a common intracellular pathway in SGNs, a candidate mechanism to regulate neuronal excitability of SGNs.
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire de l'Audition, Institut National de la Santé et de la Recherche Médicale EMI 99-27, Université de Bordeaux 2, Hôpital Pellegrin, 33076 Bordeaux, France.
authors.forename: Ken
authors.initials: K
authors.lastname: Ito
authors.forename: Didier
authors.initials: D
authors.lastname: Dulon
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017136:Ion Transport / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D058914:Purinergic Antagonists; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013136:Spiral Ganglion / Q000166:cytology / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology
chemical_list: D002412:Cations; D002614:Chelating Agents; D007476:Ionophores; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D058914:Purinergic Antagonists; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D004533:Egtazic Acid; D015759:Ionomycin; D013498:Suramin; D009538:Nicotine; D001285:Atropine; D009116:Muscarine; D000255:Adenosine Triphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000109:Acetylcholine; D002118:Calcium