Submit a comment

Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
Irene L. Ennis, … , Eduardo Marbán, H. Bradley Nuss
Irene L. Ennis, … , Eduardo Marbán, H. Bradley Nuss
Published February 1, 2002
Citation Information: J Clin Invest. 2002;109(3):393-400. https://doi.org/10.1172/JCI13359.
View: Text | PDF
Article

Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility

Abstract

Heart failure is characterized by depressed contractility and delayed repolarization. The latter feature predisposes the failing heart to ventricular arrhythmias and represents a logical target for gene therapy. Unfortunately, unopposed correction of the delay in repolarization will decrease the time available for calcium cycling during each heartbeat, potentially aggravating the depression of contractility. Here we describe the development and application of a novel gene therapy strategy designed to abbreviate excitation without depressing contraction. The calcium ATPase SERCA1 was coexpressed with the potassium channel Kir2.1 in guinea pig hearts. Myocytes from the hearts had bigger calcium transients and shorter action potentials. In vivo, repolarization was abbreviated, but contractile function remained unimpaired. Dual gene therapy of the sort described here can be generalized to exploit opposing or synergistic therapeutic principles to achieve a tailored phenotype.

Authors

Irene L. Ennis, Ronald A. Li, Anne M. Murphy, Eduardo Marbán, H. Bradley Nuss

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required