E Etienne Verheijck1, Ronald Wilders, Lennart N Bouman. 1. Academic Medical Center, Department of Physiology, Task Force Heart Failure and Aging, University of Amsterdam, The Netherlands. e.verheijck@amc.uva.nl
Abstract
BACKGROUND: Proper pacemaking of the heart requires a specific organization of the sinoatrial (SA) node. The SA node drives the surrounding atrium but needs to be protected from its hyperpolarizing influence, which tends to suppress pacemaker activity. It has been suggested that the hyperpolarizing atrial influence is minimal at the site of the central nodal area. METHODS AND RESULTS: Atrio-sinus interaction was assessed by specific depolarization of the SA node by blocking the HERG-encoded rapid delayed rectifier current (I(K,r)) with the drug E-4031. In the SA node, E-4031 (1 micromol/L) changed action potential configuration drastically but never resulted in pacemaker arrest. In the atrium, E-4031 did not affect the membrane resting potential, thereby leaving the normal hyperpolarizing load on the SA node intact. When the SA node was sectioned into strips and subsequently separated from the atrium, spontaneous electrical activity of the strip containing the primary pacemaker ceased on I(K,r) blockade. When not separated from the atrium, I(K,r) blockade never resulted in pacemaker arrest. A similar effective atrio-sinus interaction was demonstrated in computer simulations. CONCLUSIONS: Our results demonstrate that the atrium provides an effective hyperpolarizing load on the central SA nodal area and is at least one of the controlling mechanisms for normal pacemaking function. The present study can be of help in understanding why patients with long-QT2 syndrome secondary to a mutation in HERG do not show sinus arrest.
BACKGROUND: Proper pacemaking of the heart requires a specific organization of the sinoatrial (SA) node. The SA node drives the surrounding atrium but needs to be protected from its hyperpolarizing influence, which tends to suppress pacemaker activity. It has been suggested that the hyperpolarizing atrial influence is minimal at the site of the central nodal area. METHODS AND RESULTS: Atrio-sinus interaction was assessed by specific depolarization of the SA node by blocking the HERG-encoded rapid delayed rectifier current (I(K,r)) with the drug E-4031. In the SA node, E-4031 (1 micromol/L) changed action potential configuration drastically but never resulted in pacemaker arrest. In the atrium, E-4031 did not affect the membrane resting potential, thereby leaving the normal hyperpolarizing load on the SA node intact. When the SA node was sectioned into strips and subsequently separated from the atrium, spontaneous electrical activity of the strip containing the primary pacemaker ceased on I(K,r) blockade. When not separated from the atrium, I(K,r) blockade never resulted in pacemaker arrest. A similar effective atrio-sinus interaction was demonstrated in computer simulations. CONCLUSIONS: Our results demonstrate that the atrium provides an effective hyperpolarizing load on the central SA nodal area and is at least one of the controlling mechanisms for normal pacemaking function. The present study can be of help in understanding why patients with long-QT2 syndrome secondary to a mutation in HERG do not show sinus arrest.
Authors: Eric D Larson; Joshua R St Clair; Whitney A Sumner; Roger A Bannister; Cathy Proenza Journal: Proc Natl Acad Sci U S A Date: 2013-10-15 Impact factor: 11.205
Authors: Yael Yaniv; Alexey E Lyashkov; Syevda Sirenko; Yosuke Okamoto; Toni-Rose Guiriba; Bruce D Ziman; Christopher H Morrell; Edward G Lakatta Journal: J Mol Cell Cardiol Date: 2014-09-22 Impact factor: 5.000