BACKGROUND: Atrial fibrillation (AF) is associated with increased 
inward-rectifier current activity that may stabilize atrial rotors maintaining 
the arrhythmia. Left atrial (LA) structures are important for AF maintenance, 
but previous studies have mostly evaluated changes in the right atrium. 
MicroRNA-1 (miR-1) reciprocally regulates inwardly rectifying potassium channel 
(Kir)2.1 expression in coronary disease, contributing to arrhythmogenesis.
OBJECTIVES: This study sought to evaluate changes in miR-1 and Kir2 subunit 
expression in relation to I(K1) alterations in LA of patients with persistent 
AF.
METHODS: Atrial tissue was obtained from 62 patients (31 with AF) undergoing 
mitral valve repair or bypass grafting. Currents were recorded from isolated 
cells. Proteins were quantified from immunoblots. mRNA and miR-1 levels were 
measured with real-time polymerase chain reaction. Immunohistochemistry was 
applied to localize connexin (Cx) 43.
RESULTS: I(K1) density was increased in LA cells from patients with AF (at -100 
mV: -5.9 +/- 1.3 vs. -2.7 +/- 0.7 sinus rhythm, P <.05). There was a 
corresponding increase in Kir2.1 protein expression, but no change in other Kir 
or Cx proteins. Expression of inhibitory miR-1 was reduced by approximately 86% 
in tissue samples of AF patients. Kir2.1 mRNA was significantly increased. No 
change in Cx43 localization occurred. Ex vivo tachystimulation of human atrial 
slices up-regulated Kir2.1 and down-regulated miR-1, suggesting a primary role 
of atrial rate in miR-1 down-regulation and I(K1) up-regulation.
CONCLUSION: miR-1 levels are greatly reduced in human AF, possibly contributing 
to up-regulation of Kir2.1 subunits, leading to increased I(K1). Because 
up-regulation of inward-rectifier currents is important for AF maintenance, 
these results provide potential new insights into molecular mechanisms of AF 
with potential therapeutic implications.