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

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Susanne Edeling Hede Klærke, Jan Amstrup, Dan Arne Klærke, Ivana Novak

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 Ca(2+)-activated K+ channels of intermediate conductance (IK) and big conductance (BK), but not small conductance (SK). Possible interactions between P2Y receptors and these Ca(2+)-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 activ ation of currents by UTP, respectively. Taken together, this study shows that there are different interactions between the subtypes of P2Y purinergic receptors and different Ca(2+)-activated K+ channels.
Original languageEnglish
JournalPflügers Archiv - European Journal of Physiology
Volume450
Issue number6
Pages (from-to)429-436
Number of pages8
ISSN0031-6768
DOIs
Publication statusPublished - 2005

Bibliographical note

Keywords: Animals; Female; Intermediate-Conductance Calcium-Activated Potassium Channels; Large-Conductance Calcium-Activated Potassium Channels; Oocytes; Pancreatic Ducts; Potassium Channels, Calcium-Activated; Rats; Rats, Wistar; Receptors, Purinergic P2; Reverse Transcriptase Polymerase Chain Reaction; Small-Conductance Calcium-Activated Potassium Channels; Uridine Triphosphate; Xenopus laevis

    Research areas

  • LIFE - Maxi K, KCNMA1, SK4, KCNN4, Pancreas, Purinergic receptors, Ducts, Slo

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