Molecular Basis of Downregulation of G-Protein–Coupled Inward Rectifying K⁺Current (<b><i>I</i></b>_K,ACh) in Chronic Human Atrial Fibrillation

Abstract

Chronic human AF induces transcriptionally mediated upregulation of I(K1) but downregulation of I(K,ACh) and attenuates the muscarinic receptor-mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating I(K,ACh) to counteract the shortening of the atrial effective refractory period due to electrical remodeling.