Submitted on August 16, 2004
Accepted on May 9, 2005
Effects of Hyperthyroidism on Delayed Rectifier Potassium Currents in Left and Right Murine Atrium
Ying Hu1, S.V. Penelope Jones2, and Wolfgang H Dillmann1*
1 Medicine, University of California, San Diego, La Jolla, CA, USA
2 Psychiatry, University of California, San Diego, La Jolla, CA, USA
* To whom correspondence should be addressed. E-mail: wdillmann{at}ucsd.edu.
Hyperthyroidism has been associated with atrial fibrillation (AF), however, hyperthyroidism induced ion channel changes which may predispose to AF have not been fully elucidated. To understand the electrophysiological changes occurring in left and right atrium with hyperthyroidism, the patch-clamp technique was utilized to compare action potential duration (APD) and whole cell currents in myocytes from left and right atria from both control and hyperthyroid mice. Additionally, RNase protection assays and immunoblotting were performed to evaluate the mRNA and protein expression levels of potassium channel alpha subunits in left and right atrium. The results showed that: (1) In control mice, the APD was shorter and the ultra-rapid delayed rectifier potassium conductance (Ikur) and the sustained delayed rectifier potassium conductance (ISS) were larger in the left atrium than in the right. The mRNA and protein expression levels of Kv1.5 and Kv2.1 were also higher in the left atrium. (2) In hyperthyroid mice, the APD was shortened and both IKur and ISS were increased in both left and right atrial myocytes. The protein expression levels of Kv1.5 and Kv2.1 were increased significantly in both atria from hyperthyroid mice. (3) The influence of hyperthyroidism on APD and delayed rectifier potassium currents was more prominent in right atrium than in the left, which minimized the inter-atrial APD difference. In conclusion, hyperthyroidism resulted in a more significant APD shortening and greater delayed rectifier potassium current increases in the right versus the left atrium, which can contribute to the propensity for atrial arrhythmia in the hyperthyroid heart.
