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P2Y2 and P2Y4 receptors regulate pancreatic Ca2+-activated K+ channels differently

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Abstract

Extracellular ATP is an important regulator of transepithelial transport in a number of tissues. In pancreatic ducts, we have shown that ATP modulates epithelial K+ channels via purinergic receptors, most likely the P2Y2 and P2Y4 receptors, but the identity of the involved K+ channels was not clear. In this study, we show by RT-PCR analysis that rat pancreatic ducts express Ca2+-activated K+ channels of intermediate conductance (IK) and big conductance (BK), but not small conductance (SK). Possible interactions between P2Y receptors and these Ca2+-activated K+ channels were examined in co-expression experiments in Xenopus laevis oocytes. K+ channel activity was measured electrophysiologically in oocytes stimulated with UTP (0.1 mM). UTP stimulation of oocytes expressing P2Y4 receptors and BK channels resulted in a 30% increase in the current through the expressed channels. In contrast, stimulation of P2Y2 receptors led to a 20% inhibition of co-expressed BK channel activity, a response that was sensitive to TEA. Furthermore, co-expression of IK channels with P2Y4 and P2Y2 receptors resulted in a large hyperpolarization and 22-fold and 5-fold activation of currents by UTP, respectively. Taken together, this study shows that there are different interactions between the subtypes of P2Y purinergic receptors and different Ca2+-activated K+ channels.

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Acknowledgments

We are most grateful to T.K. Harden (University of North Carolina) for providing us with cDNA for human P2Y2 and P2Y4 receptors and E.H. Larsen for a loan of oocyte clamp equipment. S.E. Hede was supported by The Lundbeck Foundation and Augustinus Fonden. The project was supported by the Danish Research Councils (grants 22-011-0318 and 21-03-0558). We are grateful to Alice Q.C. Scheuer for expert handling of the animals. Technical assistance of Anni V. Olsen, Birthe Petersen, Arne Nielsen, Tove Soland and Birthe Lynderup is also gratefully acknowledged.

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Authors and Affiliations

  1. Institute of Molecular Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen Ø, Denmark

    Susanne E. Hede, Jan Amstrup & Ivana Novak

  2. Section for Physiology and Biochemistry, The Royal Veterinary and Agricultural University, Copenhagen, Denmark

    Dan A. Klaerke

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  1. Susanne E. Hede
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  2. Jan Amstrup
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  4. Ivana Novak
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Correspondence to Ivana Novak.

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Hede, S.E., Amstrup, J., Klaerke, D.A. et al. P2Y2 and P2Y4 receptors regulate pancreatic Ca2+-activated K+ channels differently. Pflugers Arch - Eur J Physiol 450, 429–436 (2005). https://doi.org/10.1007/s00424-005-1433-3

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  • DOI: https://doi.org/10.1007/s00424-005-1433-3

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