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The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation.

Mesirca P, Marger L, Toyoda F, Rizzetto R, Audoubert M, Dubel S, Torrente AG, Difrancesco ML, Muller JC, Leoni AL, Couette B, Nargeot J, Clapham DE, Wickman K, Mangoni ME.

J Gen Physiol. 2013 Aug;142(2):113-26. doi: 10.1085/jgp.201310996. Epub 2013 Jul 15.


RGS4 regulates parasympathetic signaling and heart rate control in the sinoatrial node.

Cifelli C, Rose RA, Zhang H, Voigtlaender-Bolz J, Bolz SS, Backx PH, Heximer SP.

Circ Res. 2008 Aug 29;103(5):527-35. doi: 10.1161/CIRCRESAHA.108.180984. Epub 2008 Jul 24.


RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate.

Wydeven N, Posokhova E, Xia Z, Martemyanov KA, Wickman K.

J Biol Chem. 2014 Jan 24;289(4):2440-9. doi: 10.1074/jbc.M113.520742. Epub 2013 Dec 6.


Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice.

Krishnaswamy PS, Egom EE, Moghtadaei M, Jansen HJ, Azer J, Bogachev O, Mackasey M, Robbins C, Rose RA.

J Mol Cell Cardiol. 2015 May;82:125-35. doi: 10.1016/j.yjmcc.2015.02.024. Epub 2015 Mar 6.


Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability.

Posokhova E, Ng D, Opel A, Masuho I, Tinker A, Biesecker LG, Wickman K, Martemyanov KA.

PLoS One. 2013 Oct 29;8(10):e76973. doi: 10.1371/journal.pone.0076973. eCollection 2013.


Glycogen synthase kinase-3β inhibition ameliorates cardiac parasympathetic dysfunction in type 1 diabetic Akita mice.

Zhang Y, Welzig CM, Picard KL, Du C, Wang B, Pan JQ, Kyriakis JM, Aronovitz MJ, Claycomb WC, Blanton RM, Park HJ, Galper JB.

Diabetes. 2014 Jun;63(6):2097-113. doi: 10.2337/db12-1459. Epub 2014 Jan 23.


Genetic inhibition of Na+-Ca2+ exchanger current disables fight or flight sinoatrial node activity without affecting resting heart rate.

Gao Z, Rasmussen TP, Li Y, Kutschke W, Koval OM, Wu Y, Wu Y, Hall DD, Joiner ML, Wu XQ, Swaminathan PD, Purohit A, Zimmerman K, Weiss RM, Philipson KD, Song LS, Hund TJ, Anderson ME.

Circ Res. 2013 Jan 18;112(2):309-17. doi: 10.1161/CIRCRESAHA.111.300193. Epub 2012 Nov 27.


Number and stoichiometry of subunits in the native atrial G-protein-gated K+ channel, IKACh.

Corey S, Krapivinsky G, Krapivinsky L, Clapham DE.

J Biol Chem. 1998 Feb 27;273(9):5271-8.


Deep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4.

Baruscotti M, Bucchi A, Viscomi C, Mandelli G, Consalez G, Gnecchi-Rusconi T, Montano N, Casali KR, Micheloni S, Barbuti A, DiFrancesco D.

Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1705-10. doi: 10.1073/pnas.1010122108. Epub 2011 Jan 10.


GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels.

Kennedy ME, Nemec J, Corey S, Wickman K, Clapham DE.

J Biol Chem. 1999 Jan 22;274(4):2571-82.


HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes.

Nobles M, Sebastian S, Tinker A.

Pflugers Arch. 2010 Jun;460(1):99-108. doi: 10.1007/s00424-010-0799-z. Epub 2010 Feb 26.


RGS6/Gβ5 complex accelerates IKACh gating kinetics in atrial myocytes and modulates parasympathetic regulation of heart rate.

Posokhova E, Wydeven N, Allen KL, Wickman K, Martemyanov KA.

Circ Res. 2010 Nov 26;107(11):1350-4. doi: 10.1161/CIRCRESAHA.110.224212. Epub 2010 Sep 30. Erratum in: Circ Res. 2011 Feb 4;108(3):e3.


Functional anatomy of the murine sinus node: high-resolution optical mapping of ankyrin-B heterozygous mice.

Glukhov AV, Fedorov VV, Anderson ME, Mohler PJ, Efimov IR.

Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H482-91. doi: 10.1152/ajpheart.00756.2009. Epub 2010 Jun 4.


Gbeta binding to GIRK4 subunit is critical for G protein-gated K+ channel activation.

Krapivinsky G, Kennedy ME, Nemec J, Medina I, Krapivinsky L, Clapham DE.

J Biol Chem. 1998 Jul 3;273(27):16946-52.


The mechanism of increased postnatal heart rate and sinoatrial node pacemaker activity in mice.

Adachi T, Shibata S, Okamoto Y, Sato S, Fujisawa S, Ohba T, Ono K.

J Physiol Sci. 2013 Mar;63(2):133-46. doi: 10.1007/s12576-012-0248-1. Epub 2013 Jan 4.


Functional role of CLC-2 chloride inward rectifier channels in cardiac sinoatrial nodal pacemaker cells.

Huang ZM, Prasad C, Britton FC, Ye LL, Hatton WJ, Duan D.

J Mol Cell Cardiol. 2009 Jul;47(1):121-32. doi: 10.1016/j.yjmcc.2009.04.008. Epub 2009 Apr 17.


Abnormal heart rate regulation in GIRK4 knockout mice.

Wickman K, Nemec J, Gendler SJ, Clapham DE.

Neuron. 1998 Jan;20(1):103-14.


A rapidly activating delayed rectifier K+ current regulates pacemaker activity in adult mouse sinoatrial node cells.

Clark RB, Mangoni ME, Lueger A, Couette B, Nargeot J, Giles WR.

Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1757-66. Epub 2003 Dec 23.


Control of heart rate by cAMP sensitivity of HCN channels.

Alig J, Marger L, Mesirca P, Ehmke H, Mangoni ME, Isbrandt D.

Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12189-94. doi: 10.1073/pnas.0810332106. Epub 2009 Jul 1.

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