TY - JOUR
T1 - Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis
AU - Fakler, B.
AU - Brändle, U.
AU - Glowatzki, E.
AU - Zenner, H. P.
AU - Ruppersberg, J. P.
N1 - Funding Information:
All correspondence should be addressed to J. P. R. We would like to thank Prof. Dr. A. Gummer and D. Colquhoun, Drs. A. Gibb, M. H~iusser, L. Wollmuth, J. Mosbacher, and U. Rexhausen for reading the manuscript, Prof. Dr. R. Penner and Prof. Dr. J. Hescheler for helpful discussions, Mrs. C. K6nig and Mrs. S. Weidemann for molecular cloning and RNA synthesis, and Mrs. M. Ruppersberg for graphical support. This work was supported by the Deutsche Forschungsgemeinschaft (KliFo H6rforschung; Ze149/6-1).
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1994/12
Y1 - 1994/12
N2 - Second messenger regulation of IRK1(Kir2.1) inward rectifier K+ channels was investigated in giant inside-out patches from Xenopus oocytes. Kir2.1-mediated currents that run down completely within minutes upon excision of the patches could be partly restored by application of Mg-ATP together with >10 μM free Mg2+ to the cytoplasmic side of the patch. As restoration could not be induced by the ATP analogs AMP-PNP or ATPγS, this suggests an ATPase-like mechanism. In addition to ATP, the catalytic subunit of cAMP-dependent protein kinase (PKA) induced an increase in current amplitude, which could, however, only be observed if channels were previously or subsequently stimulated by Mg-ATP and free Mg2+. This indicates that functional activity of Kir2.1 channels requires both phosphorylation by PKA and ATP hydrolysis. Moreover, currents could be down-regulated by N-heptyl-5-chloro-l-nap hthalenesulfonamide, a specific stimulator of protein kinase C (PKC), suggesting that PKA and PKC mediate inverse effects on Kir2.1 channels. Regulation of Kir2.1 channels described here may be an important mechanism for regulation of excitability.
AB - Second messenger regulation of IRK1(Kir2.1) inward rectifier K+ channels was investigated in giant inside-out patches from Xenopus oocytes. Kir2.1-mediated currents that run down completely within minutes upon excision of the patches could be partly restored by application of Mg-ATP together with >10 μM free Mg2+ to the cytoplasmic side of the patch. As restoration could not be induced by the ATP analogs AMP-PNP or ATPγS, this suggests an ATPase-like mechanism. In addition to ATP, the catalytic subunit of cAMP-dependent protein kinase (PKA) induced an increase in current amplitude, which could, however, only be observed if channels were previously or subsequently stimulated by Mg-ATP and free Mg2+. This indicates that functional activity of Kir2.1 channels requires both phosphorylation by PKA and ATP hydrolysis. Moreover, currents could be down-regulated by N-heptyl-5-chloro-l-nap hthalenesulfonamide, a specific stimulator of protein kinase C (PKC), suggesting that PKA and PKC mediate inverse effects on Kir2.1 channels. Regulation of Kir2.1 channels described here may be an important mechanism for regulation of excitability.
UR - http://www.scopus.com/inward/record.url?scp=0028670803&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028670803&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(94)90426-X
DO - 10.1016/0896-6273(94)90426-X
M3 - Article
C2 - 7993632
AN - SCOPUS:0028670803
SN - 0896-6273
VL - 13
SP - 1413
EP - 1420
JO - Neuron
JF - Neuron
IS - 6
ER -