Atrial tachypacing increased sinoatrial node recovery time by approximately 70% (P<0.01) and reduced densities of the HCN-related funny current by approximately 48% (P<0.001).
Does atrial tachypacing impair sinoatrial node function by altering ion channel expression in a canine model?
Atrial tachyarrhythmia downregulates sinoatrial node HCN2/4 and minK subunit expression and corresponding currents, providing a mechanistic basis for tachycardia-induced sinus node dysfunction.
p-value: p=<0.01
BACKGROUND: Sinoatrial node (SAN) dysfunction is frequently associated with atrial tachyarrhythmias (ATs). Abnormalities in SAN pacemaker function after termination of ATs can cause syncope and require pacemaker implantation, but underlying mechanisms remain poorly understood. This study examined the hypothesis that ATs impair SAN function by altering ion channel expression. METHODS AND RESULTS: SAN tissues were obtained from 28 control dogs and 31 dogs with 7-day atrial tachypacing (400 bpm). Ionic currents were measured from single SAN cells with whole-cell patch-clamp techniques. Atrial tachypacing increased SAN recovery time in vivo by approximately 70% (P50% (P<0.01) and for the beta-subunit minK by approximately 42% (P<0.05). SAN transcript expression for the rapid delayed-rectifier (I(Kr)) alpha-subunit ERG, the slow delayed-rectifier (I(Ks)) alpha-subunit KvLQT1, the beta-subunit MiRP1, the L-type (I(CaL)) and T-type (I(CaT)) Ca2+-current subunits Cav1.2 and Cav3.1, and the gap-junction subunit connexin 43 (were unaffected by atrial tachypacing. Atrial tachypacing reduced densities of the HCN-related funny current (I(f)) and I(Ks) by approximately 48% (P<0.001) and approximately 34% (P<0.01), respectively, with no change in voltage dependence or kinetics. I(Kr), I(CaL), and I(CaT) were unaffected. SAN cells lacked Ba2+-sensitive inward-rectifier currents, irrespective of AT. SAN action potential simulations that incorporated AT-induced alterations in I(f) accounted for slowing of periodicity, with no additional contribution from changes in I(Ks). CONCLUSIONS: AT downregulates SAN HCN2/4 and minK subunit expression, along with the corresponding currents I(f) and I(Ks). Tachycardia-induced remodeling of SAN ion channel expression, particularly for the "pacemaker" subunit I(f), may contribute to the clinically significant association between SAN dysfunction and supraventricular tachyarrhythmias.
Yeh et al. (Tue,) conducted a other in Sinoatrial node dysfunction and atrial tachyarrhythmias (n=59). Atrial tachypacing vs. Control was evaluated on Sinoatrial node (SAN) recovery time in vivo (p=<0.01). Atrial tachypacing increased sinoatrial node recovery time by approximately 70% (P<0.01) and reduced densities of the HCN-related funny current by approximately 48% (P<0.001).