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

TY - JOUR

T1 - P2Y2 and P2Y4 receptors regulate pancreatic Ca²+-activated K+ channels differently

AU - Klærke, Susanne Edeling Hede

AU - Amstrup, Jan

AU - Klærke, Dan Arne

AU - Novak, Ivana

N1 - 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

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Former LIFE faculty

KW - Maxi K

KW - KCNMA1

KW - SK4

KW - KCNN4

KW - Pancreas

KW - Purinergic receptors

KW - Ducts

KW - Slo

U2 - 10.1007/s00424-005-1433-3

DO - 10.1007/s00424-005-1433-3

M3 - Journal article

C2 - 16075244

SN - 0031-6768

VL - 450

SP - 429

EP - 436

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

IS - 6

ER -