P2Y2 and P2Y4 receptors regulate pancreatic Ca(2+)-activated K+ channels differently.
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 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 Ca(2+)-activated K+ channels.
Hede
Susanne E
SE
Institute of Molecular Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen Ø, Denmark.
Amstrup
Jan
J
Klaerke
Dan A
DA
Novak
Ivana
I
D000818:Animals; D005260:Female; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010183:Pancreatic Ducts / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058473:Receptors, Purinergic P2Y2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014982:Xenopus laevis
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; C546387:P2ry2 protein, rat; D024681:Potassium Channels, Calcium-Activated; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D051640:Small-Conductance Calcium-Activated Potassium Channels; C104749:purinoceptor P2Y4; D014544:Uridine Triphosphate