The role of transient outward K+ current in electrical remodelling induced by voluntary exercise in female rat hearts.
Regular exercise can lead to electrical remodelling of the heart. The cellular mechanisms associated with these changes are not well understood, and are difficult to study in human tissue but are important given that exercise is recommended to the general population. We have investigated the role played by the transient outward K+ current (I(to)) in the changes in electrical activity seen in response to voluntary exercise training in rats. Female rats undertook 6 weeks of voluntary wheel running exercise (TRN) or were sedentary controls (SED). Monophasic action potentials (MAPs) were recorded from the surface of whole hearts. Whole cell patch clamp recordings of I(to); mRNA and protein levels of selected targets in sub-epicardial (EPI) and sub-endocardial myocardium of SED and TRN hearts were compared. In TRN rats, heart weight:body weight was significantly increased and epicardial MAPs significantly prolonged. I(to) density was reduced in TRN EPI myocytes, such that the transmural gradient of I(to) was significantly reduced (P < 0.05). Computer modelling of these changes in I(to) predicted the observed changes in action potential profile. However, transmural gradients in mRNA and protein expression for Kv4.2 or mRNA levels of the Kv4.2 regulators; KChIP2 and Irx-5 were not significantly altered by voluntary exercise. We conclude that voluntary exercise electrical remodelling is caused, at least in part, by a decrease in EPI I(to), possibly because of fewer functional channels in the membrane, which results in a fall in the transmural action potential duration gradient.
Institute of Membrane and Systems Biology and Multidisciplinary Cardiovascular Research Centre, University of Leeds, Garstang Building, Leeds LS29JT, UK.
Rachel
R
Stones
Rudolf
R
Billeter
Henggui
H
Zhang
Simon
S
Harrison
Ed
E
White
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D003198:Computer Simulation; D004699:Endocardium / Q000378:metabolism / Q000502:physiology; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000033:anatomy & histology / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology
D018398:Homeodomain Proteins; C539715:Irx5 protein, rat; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D014157:Transcription Factors; D011188:Potassium