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J Physiol Volume 558, Number 3, 793-805, August 1, 2004 DOI: 10.1113/jphysiol.2003.060186
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On the fate of skeletal myoblasts in a cardiac environment: down-regulation of voltage-gated ion channels

H. C. Ott1, S. Berjukow2, R. Marksteiner3, E. Margreiter3, G. Böck4, G. Laufer1 and S. Hering2

1 Department of Cardiac Surgery, University of Innsbruck, Austria
2 Institute of Pharmacology and Toxicology, University of Vienna, Austria
3 Institute of Biochemical Pharmacology, University of Innsbruck, Austria
4 Department of Pathophysiology, University of Innsbruck, Austria

We have analysed the voltage-gated ion channels and fusion competence of skeletal muscle myoblasts labelled with green fluorescent protein (GFP) and the membrane dye PKH transplanted into the infarcted myocardium of syngenic rats. After cell transplantation the animals were killed and GFP+–PKH+ myoblasts enzymatically isolated for subsequent studies of ionic currents through voltage-gated sodium, calcium and potassium channels. A down-regulation of all three types of ion channels after engraftment was observed. The fraction of cells with calcium (68%) and sodium channels (65%) declined to zero within 24 h and 1 week, respectively. Down-regulation of potassium currents (90% in control) occurred within 2 weeks to about 30%. Before injection myoblasts expressed predominantly transient outward potassium channels whereas after isolation from the myocardium exclusively rapid delayed rectifier channels. The currents recovered completely between 1 and 6 weeks under cell culture conditions. The down-regulation of ion channels and changes in potassium current kinetics suggest that the environment provided by infarcted myocardium affects expression of voltage-gated ion channels of skeletal myoblasts.

(Received 20 December 2003; accepted after revision 4 June 2004; first published online 11 June 2004)
Corresponding author S. Hering: Institute of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A-1090 Vienna. Email: steffen.hering{at}univie.ac.at


H. C. Ott and S. Berjukow contributed equally to this work




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