Muscarinic modulation of erg potassium current

The Journal of Physiology
Wiebke HirdesBertil Hille

Abstract

We studied modulation of current in human embryonic kidney tsA-201 cells coexpressing rat erg1 channels with M(1) muscarinic receptors. Maximal current was inhibited 30% during muscarinic receptor stimulation, with a small positive shift of the midpoint of activation. Inhibition was attenuated by coexpression of the regulator of G-protein signalling RGS2 or of a dominant-negative protein, G(q), but not by N-ethylmaleimide or C3 toxin. Overexpression of a constitutively active form of G(q) (but not of G(13) or of G(s)) abolished the erg current. Hence it is likely that G(q/11), and not G(i/o) or G(13), mediates muscarinic inhibition. Muscarinic suppression of erg was attenuated by chelating intracellular Ca(2+) to < 1 nm free Ca(2+) with 20 mm BAPTA in the pipette, but suppression was normal if internal Ca(2+) was strongly clamped to a 129 nm free Ca(2+) level with a BAPTA buffer and this was combined with numerous other measures to prevent intracellular Ca(2+) transients (pentosan polysulphate, preincubation with thapsigargin, and removal of extracellular Ca(2+)). Hence a minimum amount of Ca(2+) was necessary for the inhibition, but a Ca(2+) elevation was not. The ATP analogue AMP-PCP did not prevent inhibition. The protein ki...Continue Reading

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Citations

Jul 12, 2007·Pflügers Archiv : European journal of physiology·Jin-Song Bian, Thomas V McDonald
Aug 19, 2009·Pflügers Archiv : European journal of physiology·Wiebke HirdesChristiane K Bauer
Apr 17, 2010·Pflügers Archiv : European journal of physiology·Diomedes E LogothetisRahul Mahajan
Jun 1, 2005·Current Opinion in Neurobiology·Byung-Chang Suh, Bertil Hille
Sep 1, 2005·The Journal of General Physiology·Lisa F HorowitzBertil Hille
Jan 29, 2005·The Journal of Physiology·Wiebke HirdesJürgen R Schwarz
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Nov 5, 2014·Journal of Pharmacological Sciences·Masayuki X Mori, Ryuji Inoue
Apr 7, 2012·Cellular Signalling·Carlos A Villalba-Galea
Aug 3, 2013·Channels·Martin Kruse, Bertil Hille
Oct 9, 2014·Annual Review of Physiology·Diomedes E LogothetisLia Baki
Jun 15, 2007·Nature Neuroscience·Mircea IftincaGerald W Zamponi
Nov 1, 2007·Nature Reviews. Neuroscience·Nikita Gamper, Mark S Shapiro
Jul 9, 2020·Frontiers in Pharmacology·Carlos A Villalba-Galea
Sep 20, 2012·Physiological Reviews·Jamie I VandenbergAdam P Hill
Sep 2, 2006·The Journal of Pharmacology and Experimental Therapeutics·Catherine M McKay, Jan D Huizinga

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