The chronic treatment of patients with a beta-blocker is associated with a prolongation of the atrial cell action potential duration1. The transient outward K+ current (ITO) density is reduced in these patients but there is no change in the voltage or time dependent properties of this current2. The mechanisms underlying this reduction in ITO density are unknown. To test the hypothesis that the expression of atrial ITO channel pore-forming and accessory subunits differs between patients treated or not treated with a beta-blocker. Right atrial appendage tissue was obtained from 36 consenting patients, in sinus rhythm, undergoing cardiac surgery. Of these patients, 16 were taking beta1-selective blockers for at least 4 weeks prior to surgery. Tissue mRNA and protein levels were measured using real time RT-PCR and western blotting, respectively. Chronic beta-blockade did not change the ratio of the level of mRNA encoding the ITO pore forming protein, Kv4.3, relative to 28S rRNA and GAPDH mRNA [1.8±0.1 vs 1.9±0.2, in beta-blocked (n=8) and non beta-blocked patients (n=8), respectively; mean±s.e.m. Student’s t-test, p>0.05]. Kv4.3 protein was detected in human atrial tissue at 65 kDa using a monoclonal anti-Kv4.3 antibody (Neuromab). Chronic beta-blockade did not change the ratio of the level of Kv4.3 protein relative to GAPDH [1.2±0.1 vs 1.3±0.3, in beta-blocked (n=8) and non beta-blocked patients (n=10), respectively; p>0.05). The relative levels of mRNA encoding various ITO channel accessory proteins that associate with Kv4.3 were unchanged in beta-blocked (n=8) compared to non beta-blocked (n=8) patients: KChIP2 (2.5±0.3 vs 2.7±0.6); KChAP (2.5±v0.1 vs 2.4±0.2); Kvβ1 (3.8±0.2 vs 3.2±0.4); Kvβ2 (1.9±0.1 vs 1.7±0.3) and frequenin (2.0±0.2 vs 1.9±0.3); p>0.05 for each. The reduction in atrial ITO density associated with the chronic treatment of patients with a beta-blocker cannot be explained by changes in the expression of the ion channel pore-forming subunit or by changes in the expression of its regulatory accessory subunit genes.
University of Manchester (2007) Proc Physiol Soc 8, PC20
Poster Communications: Reduction of human atrial ITO by chronic beta-blockade is not due to changes in ion channel expression
G. E. Marshall1, J. O. Tellez2, J. A. Russell1, S. Currie3, M. R. Boyett2, A. C. Rankin1, K. A. Kane3, A. J. Workman1
1. Cardiovascular Medicine, University of Glasgow, Glasgow, United Kingdom. 2. University of Manchester, Manchester, United Kingdom. 3. University of Strathclyde, Glasgow, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.