Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis

B. Fakler, U. Brändle, E. Glowatzki, H. P. Zenner, J. P. Ruppersberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1413-1420
Number of pages8
JournalNeuron
Volume13
Issue number6
DOIs
StatePublished - Dec 1994
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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