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(Circulation Research. 1999;85:661-662.)
© 1999 American Heart Association, Inc.

Editorial

Gap Junctional Conductance in Cardiomyopathic Hamsters

The Role of c-Src

Walmor C. De Mello

From the Department of Pharmacology, School of Medicine, University of Puerto Rico, San Juan.

Correspondence to Walmor C. De Mello, MD, PhD, Department of Pharmacology, 3rd Floor, A-319, Main Building, Medical Sciences Campus, Medical Center, Bo. Monacillo, Rio Piedras, Puerto Rico 00935-00927. E-mail w_mello@rcmaca.upr.clu.edu

Key Words: junction conductance • hamster • cardiomyopathy • c-Src

	Introduction

 
Gap junctions, which are small hydrophilic channels connecting apposing cardiac cells, play an important role on the electrical and mechanical synchronization in heart muscle.¹ Gap junctional proteins are arranged in a hexagonal array,^{2 3} and each protein consists of a pair of hemichannels (connexons), one from each cell.⁴ The junctional conductance is modulated by several factors including Ca²⁺_i and second messengers such as cAMP and cGMP.^{5 6 7} Second messengers influence the junctional conductance through the phosphorylation of junctional proteins.^{7 8} The activation of cAMP-dependent protein kinase (PKA), for instance, increases junctional conductance in cardiac muscle, an effect suppressed by intracellular dialysis of a PKA inhibitor.⁹ The role of gap junctions in heart failure merits close scrutiny, given the high prevalence of conduction disorders such as intraventricular conduction delays in patients with cardiomyopathy. The complexity and diversity of human heart failure, along with the obvious limitations of work with human subjects, motivate the investigation of the molecular basis of conduction abnormalities in animal models of heart failure.

In cardiomyopathic hamsters, which mirror many aspects of cardiomyopathy and heart failure in humans,¹⁰ interstitial fibrosis, necrosis, and calcification are extensively distributed throughout the ventricle, particularly at an advanced stage of the disease.¹¹ The distribution of connexin 43, the most abundant connexin in cardiac muscle,⁴ is diffuse, and the structure of the intercalated discs is irregular.¹² According to some authors,¹² the expression of connexin 43 is not changed in cardiomyopathic hamsters.

Recent studies performed in isolated ventricular cell pairs from cardiomyopathic hamsters (BIO TO2) indicated that the . . . [Full Text of this Article]