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 Ϸ70% (PϽ0.01), a change which reflects impaired SAN function. In dogs that underwent atrial tachypacing, SAN mRNA expression (real-time reverse-transcription polymerase chain reaction) was reduced for hyperpolarization-activated cyclic nucleotide-gated subunits (HCN2 and HCN4) by Ͼ50% (PϽ0.01) and for the ␤-subunit minK by Ϸ42% (PϽ0.05). SAN transcript expression for the rapid delayed-rectifier (I Kr ) ␣-subunit ERG, the slow delayed-rectifier (I Ks ) ␣-subunit KvLQT1, the ␤-subunit MiRP1, the L-type (I CaL ) and T-type (I CaT ) Ca 2ϩ -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 Ϸ48% (PϽ0.001) and Ϸ34% (PϽ0.01), respectively, with no change in voltage dependence or kinetics. I Kr , I CaL , and I CaT were unaffected. SAN cells lacked Ba 2ϩ -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