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. 2003 Mar 4;107(8):1106-9.
doi: 10.1161/01.cir.0000059939.97249.2c.

Expression and function of a biological pacemaker in canine heart

Jihong Qu  1 , Alexei N Plotnikov, Peter Danilo Jr, Iryna Shlapakova, Ira S Cohen, Richard B Robinson, Michael R Rosen
Affiliations

Expression and function of a biological pacemaker in canine heart

Jihong Qu et al. Circulation. .

Abstract

Background: We hypothesized that localized overexpression of the hyperpolarization-activated, cyclic nucleotide-gated (HCN2) pacemaker current isoform in canine left atrium (LA) would constitute a novel biological pacemaker.

Methods and results: Adenoviral constructs of mouse HCN2 and green fluorescent protein (GFP) or GFP alone were injected into LA, terminal studies performed 3 to 4 days later, hearts removed, and myocytes examined for native and expressed pacemaker current (I(f)). Spontaneous LA rhythms occurred after vagal stimulation-induced sinus arrest in 4 of 4 HCN2+GFP dogs and 0 of 3 GFP dogs (P<0.05). Native I(f) in nonexpressed atrial myocytes was 7+/-4 pA at -130 mV (n=5), whereas HCN2+GFP LA had expressed pacemaker current (I(HCN2)) of 3823+/-713 pA at -125 mV (n=10) and 768+/-365 pA at -85 mV.

Conclusions: HCN2 overexpression provides an I(f)-based pacemaker sufficient to drive the heart when injected into a localized region of atrium, offering a promising gene therapy for pacemaker disease.

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