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P2Y1 receptors are linked to KCa2 channels in PC12 cells


P2Y1 receptors are widely expressed in the brain, but their signalling mechanisms in neurons remained largely unknown. In sympathetic neurons, recombinant P2Y1 receptors inhibit voltage-gated Ca2+ currents (ICa) and M-type K+ currents.


Patch-clamp recordings were performed in PC12 cell cultures, P2Y receptor ligands and signaling interceptors were applied.


In PC12 cells stably expressing rat P2Y1 receptors (PC12-P2Y1), but not in wild type PC12 cells (PC12-wt), ADP induced rises in intracellular Ca2+ with half-maximal effects at 15 ± 1.3 μM. In whole-cell patch-clamp recordings, ADP inhibited ICa of PC12-P2Y1 cells (EC50: 6.3 ± 1.7 μM) and of PC12-wt (EC50: 3.8 ± 1.3 μM); this effect was not altered by the P2Y1 antagonist MRS 2216 (1 μM), but abolished by P2Y12 antagonists. In perforated-patch recordings, ADP inhibited IM relaxation amplitudes of PC12-P2Y1 cells with half-maximal effects at 2.0 ± 1.8 μM, but in PC12-wt no such effect was observed. In PC12-P2Y1, but not in PC12-wt cells, ADP (1-100 μM) caused transient increases in outward currents determined at -30 mV in the perforated-patch, but not the whole-cell mode. ADP-induced currents had reversal potentials between -80 and -90 mV which was close to the calculated K+ equilibrium potential (-89 mV). Replacement of 100 mM extracellular Na+ by K+ shifted the reversal potential of ADP-induced currents to about -10 mV which was again close to the K+ equilibrium potential (-17 mV). ADP-induced currents were prevented by thapsigargin (1 μM) and by the phospholipase C inhibitor U73122 (3 μM), but not by an inactive analogue. Finally, the ADP-induced currents were significantly reduced by 100 nM apamin.


These results reveal channels of the KCa2 family as novel targets for P2Y1 receptor signalling.


Supported by FWF.

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Correspondence to Stefan Boehm.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Schicker, K., Boehm, S. P2Y1 receptors are linked to KCa2 channels in PC12 cells. BMC Pharmacol 9 (Suppl 2), A18 (2009).

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