Molecular Physiology and Cellular Electrophysiology

Electrical signalling is central for many physiological processes, including the beating of the heart, muscle activation, thinking and homeostasis. Ion channels are expressed in virtually all cells of the body. 

In the Molecular Physiology and Cellular Electrophysiology group, we investigate ion channel function. We have excellent facilities to address ion channel function both in intact tissue, for ion channels expressed in heterologous systems including Xenopus laevis oocytes and mammalian cells lines as well as for single channels expressed in lipid bilayers. We are experts in two-electrode voltage clamp, different patch-clamp techniques and reconstitution of ion channel proteins in lipid bilayers and single channel recordings. As we host the Copenhagen site for Nanion Technologies, we have access to a fully automated high though put screening electrophysiology equipment. 

Students are always welcome to contact us for available projects. 

For research collaborations feel free to contact Professor Dan Klaerke or Kirstine Calloe.


Current projects:

Sudden Cardiac Death

We are aiming at understanding the cardiac electrophysiology in different animals as well as humans, including changes in cardiac electrophysiology that is associated with different cardiac pathologies.

  • We are investigating ionic currents in healthy and diseased hearts from humans and dogs to determine how cellular electrophysiology is affected by various cardiac diseases.
  • We are members of the Clinical Academic Group (CAG): Precision Diagnostics in Cardiology where we investigate the mechanisms underlying sudden cardiac death in humans (http://chsp.dk/precision-diagnostics-in-cardiology/).
  • We have established different models of cardiac disease and test of pharmacological compounds to predict whether they will benefit certain groups of patients.


Why do horses suddenly die?

We are members of the Equine Cardiac Group (www.ECG.ku.dk) and we have several on-going projects addressing equine cardiac electrophysiology. Horses are excellent athletes, yet, there are frequently reports of horses that suddenly die. To find out why, we are addressing the following questions:

  • Is there a hereditary component to sudden cardiac death?
  • What are the normal values for the equine ECG intervals? This needs to be established to be able to identify horses with abnormal ECGs
  • Is treatment with pharmaceutical compounds used in veterinarian medicine associated with an increased risk of cardiac arrhythmias and sudden cardiac death?
  • How a normal equine cardiac action potential is shaped?
  • Which ionic currents are of importance in equine cheat and how do they respond to adrenergic challenges? 
  • What are the coding sequences of ion channel subunits and expression levels?
  • How are equine ion channels functioning? Functional characterization of these ion channels in heterologous expression systems like Xenopus laevis oocytes or mammalian cell lines 
  • How do cloned equine ion channels respond to compounds used in veterinarian medicine? Is there a link to sudden cardiac death?


Stem cell research

Stem cells holds to promise of being used in replacement therapy, but can also be used to investigate early cellular changes, and to test pharmaceutical treatments. 

  • We have compared the electrophysiological properties
  • of fetal cardiomyocytes with those of stem cell derived cardiomyocytes.
  • We have characterized the electrophysiological properties of stem cell derived neurons from healthy individuals and from patients with different types of dementia.

Basic ion channel and receptor research

We have different projects in basic ion channel function and receptor research:

  • Volume regulation of ion channel activity
  • K+ channels as drug targets for treatment of migraine Lundbeck Foundation Res. Centre, LUCENS, Glostrup Hospital
  • K+ channels as drug targets for treatment of malaria LIFE; FARMA, SUND,  Johns Hopkins School of Medicine
  • Regulation of K+ channels by small hormone-sensitive beta-subunits, Region Sjælland
  • Receptors in parasites

Biotech and Innovation

  • We host the Copenhagen site for Nanion Technologies (Germany) 
  • We have established novel methods for expression of membrane proteins in yeast and purification of proteins. The purified protein are reconstitution into lipid bilayers and single channel currents recordings obtained. This project is part of Industrial Biomimetic Sensing and Separation (IBISS) consortium (http://www.ibiss.dtu.dk/)


Publications

  1. Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes. Tejada MA, Hashem N, Calloe K, Klaerke DA. PLoS One. 2017 Feb 21;12(2)
  2. Cell volume changes regulate slick (Slo2.1), but not slack (Slo2.2) K+ channels. Tejada MA, Stople K, Hammami Bomholtz S, Meinild AK, Poulsen AN, Klaerke DA. PLoS One. 2014 Oct 27;9(10):e110833
  3. PIP₂ modulation of Slick and Slack K⁺ channels. de los Angeles Tejada M, Jensen LJ, Klaerke DA. Biochem Biophys Res Commun. 2012 Jul 27;424(2):208-1
  4. Functional characterization of malaria parasites deficient in the K+ channel Kch2. Ellekvist P, Mlambo G, Kumar N, Klaerke DA.  Biochem Biophys Res Commun. 2017 Aug 30. pii: S0006-291X(17)31711-4
  5. High yield purification of full-length functional hERG K+ channels produced in Saccharomyces cerevisiae. Molbaek K, Scharff-Poulsen P, Helix-Nielsen C, Klaerke DA, Pedersen PA. Microb Cell Fact. 2015 Feb 7;14:15
  6. Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium. Pedersen PJ, Thomsen KB, Flak JB, Tejada MA, Hauser F, Trachsel D, Buhl R, Kalbfleisch T, DePriest MS, MacLeod JN, Calloe K, Klaerke DA. Res Vet Sci. 2017 Sep 11;113:79-86.
  7. Molecular Cloning and Functional Expression of the Equine K+ Channel KV11.1 (Ether à Go-Go-Related/KCNH2 Gene) and the Regulatory Subunit KCNE2 from Equine Myocardium. Pedersen PJ, Thomsen KB, Olander ER, Hauser F, Tejada Mde L, Poulsen KL, Grubb S, Buhl R, Calloe K, Klaerke DA. PLoS One. 2015 Sep 16;10(9):e0138320
  8. Differences in the electrocardiographic QT interval of various breeds of athletic horses during rest and exercise. Pedersen PJ, Karlsson M, Flethøj M, Trachsel DS, Kanters JK, Klaerke DA, Buhl R. J Vet Cardiol. 2016 Sep;18(3):255-64
  9. Diurnal modulation and sources of variation affecting ventricular repolarization in Warmblood horses. Pedersen PJ, Moeller SB, Flethøj M, Kanters JK, Buhl R, Klaerke DA. J Vet Cardiol. 2014 Dec;16(4):265-76.
  10. Normal electrocardiographic QT interval in race-fit Standardbred horses at rest and its rate dependence during exercise. Pedersen PJ, Kanters JK, Buhl R, Klaerke DA. J Vet Cardiol. 2013 Mar;15(1):23-3
  11. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials. Calloe K, Di Diego JM, Hansen RS, Nagle SA, Treat JA, Cordeiro JM. Biochem Pharmacol. 2016 May 15;108:36-46
  12. Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes. Calloe K, Nof E, Jespersen T, Di Diego JM, Chlus N, Olesen SP, Antzelevitch C, Cordeiro JM. J Cardiovasc Electrophysiol. 2011 Sep;22(9):1057-66.
  13. Physiological consequences of transient outward K+ current activation during heart failure in the canine left ventricle. Cordeiro JM, Calloe K, Moise NS, Kornreich B, Giannandrea D, Di Diego JM, Olesen SP, Antzelevitch C. J Mol Cell Cardiol. 2012 Jun;52(6):1291-8
  14. Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2. Lundby A, Jespersen T, Schmitt N, Grunnet M, Olesen SP, Cordeiro JM, Calloe K. Br J Pharmacol. 2010 Aug;160(8):2028-44
  15. Differential effects of the transient outward K(+) current activator NS5806 in the canine left ventricle. Calloe K, Soltysinska E, Jespersen T, Lundby A, Antzelevitch C, Olesen SP, Cordeiro JM. J Mol Cell Cardiol. 2010 Jan;48(1):191-200
  16. A transient outward potassium current activator recapitulates the electrocardiographic manifestations of Brugada syndrome. Calloe K, Cordeiro JM, Di Diego JM, Hansen RS, Grunnet M, Olesen SP, Antzelevitch C. Cardiovasc Res. 2009 Mar 1;81(4):686-94
  17. Tissue-specific effects of acetylcholine in the canine heart. Calloe K, Goodrow R, Olesen SP, Antzelevitch C, Cordeiro JM. Am J Physiol Heart Circ Physiol. 2013 Jul 1;305(1):H66-75
  18.  Characterization and mechanisms of action of novel NaV1.5 channel mutations associated with Brugada syndrome. Calloe K, Refaat MM, Grubb S, Wojciak J, Campagna J, Thomsen NM, Nussbaum RL, Scheinman MM, Schmitt N. Circ Arrhythm Electrophysiol. 2013 Feb;6(1):177-84