title: P2Y1 receptors mediate an activation of neuronal calcium-dependent K+ channels.
abstract: Molecularly defined P2Y receptor subtypes are known to regulate the functions of neurons through an inhibition of K(V)7 K(+) and Ca(V)2 Ca(2+) channels and via an activation or inhibition of Kir3 channels. Here, we searched for additional neuronal ion channels as targets for P2Y receptors. Rat P2Y(1) receptors were expressed in PC12 cells via an inducible expression system, and the effects of nucleotides on membrane currents and intracellular Ca(2+) were investigated. At a membrane potential of 30 mV, ADP induced transient outward currents in a concentration-dependent manner with half-maximal effects at 4 μm. These currents had reversal potentials close to the K(+) equilibrium potential and changed direction when extracellular Na(+) was largely replaced by K(+), but remained unaltered when extracellular Cl() was changed. Currents were abolished by P2Y(1) antagonists and by blockade of phospholipase C. ADP also caused rises in intracellular Ca(2+), and ADP-evoked currents were abolished when inositol trisphosphate-sensitive Ca(2+) stores were depleted. Blockers of K(Ca)2, but not those of K(Ca)1.1 or K(Ca)3.1, channels largely reduced ADP-evoked currents. In hippocampal neurons, ADP also triggered outward currents at 30 mV which were attenuated by P2Y(1) antagonists, depletion of Ca(2+) stores, or a blocker of K(Ca)2 channels. These results demonstrate that activation of neuronal P2Y(1) receptors may gate Ca(2+)-dependent K(+) (K(Ca)2) channels via phospholipase C-dependent increases in intracellular Ca(2+) and thereby define an additional class of neuronal ion channels as novel effectors for P2Y receptors. This mechanism may form the basis for the control of synaptic plasticity via P2Y(1) receptors.
authors.affiliation: Centre for Physiology and Pharmacology, Medical University of Vienna, A-1090 Wien, Austria.
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Schicker
authors.forename: Giri K
authors.initials: GK
authors.lastname: Chandaka
authors.forename: Petra
authors.initials: P
authors.lastname: Geier
authors.forename: Helmut
authors.initials: H
authors.lastname: Kubista
authors.forename: Stefan
authors.initials: S
authors.lastname: Boehm
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D055724:Electrophysiological Phenomena; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051656:KCNQ Potassium Channels / Q000235:genetics / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D051656:KCNQ Potassium Channels; C494842:Kcnma1 protein, rat; C491575:Kcnn4 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D024681:Potassium Channels, Calcium-Activated; D043562:Receptors, G-Protein-Coupled; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D010738:Type C Phospholipases; D011188:Potassium