Determination of P2X1alpha-sarcoglycan (adhalin) expression levels in failing human dilated cardiomyopathic left ventricles.

ABSTRACT

This study is concerned with the molecular basis of human idiopathic dilated cardiomyopathy (DCM). This disorder affects the entire heart including both atria and ventricles. It is characterized by a progressive dilatation of the ventricles and loss of contractile power that results in an impaired cardiac output. Changes in cellular levels of dystrophin have been reported in patients with muscular dystrophies (Beckers and Duchenne) which manifest as DCM. However, previous studies using Western blots dos Remedios et al., Electrophoresis 1996, 17, 235-238) of samples of left ventricles from DCM patients showed no abnormalities in dystrophin content. P2X receptors are ATP-gated cation channels located in the sarcolemma. They are upregulated by a factor of about two in the atria of DCM patients compared with nondiseased control samples. A dystrophin-associated protein, alpha-sarcoglycan, has recently been shown to be an ecto-ATPase (an extracellular ATPase) capable of regulating ATP concentrations in the space between the cardiomyocytes. In this report we examine the relationship between changes in P2X1 receptors in left ventricle samples from DCM patients and the concentration of alpha-sarcoglycan. We found no evidence for upregulation of P2X1 receptors nor was the expression of alpha-sarcoglycan significantly altered.