This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by London, B. Search for Related Content PubMed PubMed Citation Articles by London, B.

(Circulation Research. 2004;95:120.)
© 2004 American Heart Association, Inc.

Editorials

Staying Connected Without Connexin43

Can You Hear Me Now?

Barry London

From the Cardiovascular Institute, University of Pittsburgh, Pa.

Correspondence to Barry London, MD, PhD, Cardiovascular Institute, University of Pittsburgh, Scaife S572, 200 Lothrop St, Pittsburgh, PA 15213-2582. E-mail londonb@upmc.edu

See related article, pages 170–178

Key Words: connexin43 • gap junctions • arrhythmias • heart

An extract of the first 250 words of the full text is provided, because this article has no abstract.

As popular cellular telephone commercials suggest, we place considerable value on our ability to remain connected to our friends and neighbors. The same principals ring true in cardiovascular physiology. Connexin (Cx) proteins are located at cardiac gap junctions and form low resistance pathways for the intercellular spread of electrical excitation and small molecules.¹ Within each cell, six connexin subunits coassemble to form hemichannels that then dock with their counterparts on neighboring cells. Ventricular myocytes express Cx43 along with lower levels of Cx45, atrial myocytes express Cx40 and Cx43, and conduction system cells express Cx45 and Cx40. Thus, both heteromeric channels (with variable mixtures of Cx subunits in each hemichannel) and heterotypic channels (formed from asymmetric hemichannels in neighboring cells) are expected.

Gene-targeted mice have greatly advanced our understanding of the roles of individual connexin genes. Homozygous Cx45 knockout mice have abnormal cardiac development and die as embryos.² Homozygous Cx40 knockout mice have impaired conduction with prolonged PR intervals, bundle branch blocks, and a propensity toward atrial arrhythmias.³ Studies on heterozygous Cx-targeted mice (Cx43^+/–) show decreased protein levels and decreased conduction velocity, although these findings have been the subject of some controversy.⁴ Homozygous Cx43 knockout mice (Cx43^–/–) die in the early postnatal period with cardiac defects, making a detailed analysis of the impact of Cx43 ablation on ventricular impulse propagation difficult.⁵ To circumvent these difficulties, a conditional Cx43 knockout mouse using the Cre-lox system was engineered.⁶ These conditional knockout mice have marked decreases in Cx43 protein and sudden death . . . [Full Text of this Article]