Is SAP97 the main modulator of regulating Kv ion channels in dilated cardiomyopathy?

Background: Dilated cardiomyopathy is a multifactorial disease therefore it can be expected that several gene expression is altered in the heart. The exact nature of those changes has not been resolved yet. Voltage-dependent potassium channels regulate membrane excitability and cell communication between cardiomyocytes. Cardiac ion channels are assembled as a homomeric and heteromeric tetramers composed of a- and b-subunits providing the molecular basis for the transmembrane ionic currents. The synapse-associated protein 97 (SAP97) can associate with different potassium ion channels modulating and anchoring these proteins at the plasma membrane. Aim and Methods: The aim of this study was to compare the expression of Kv ion channels and the SAP97 in the cardiomyocytes of failing heart. We investigated the expression of the Kv ion channels by molecular biological techniques (real-time qPCR and immunoblotting) in the heart of failing and non-failing human ventricular preparations. Results: The a-subunits of mRNA of channels did not change significantly or we measured mild upor down-regulation. HERG and KvLQT1 were slightly up regulated but the KChIP2 gene significantly decreased 50% as the MIRP4 in the left ventricle tissues of DCM patients comparing to those of undiseased controls. Immunoblotting studies revealed that the protein expression of these a-subunits is significantly decreased in the samples of patients. Conclusion: DCM remodel the expression of delayed rectifier potassium channel genes and proteins. Down-regulation was significant in the anchoring-subunits and little changed in the pore forming a-subunits. The decreased SAP97 expression suggests that alterations in regulation of potassium ion channel expression may play a main role in the development of pathological cardiac repolarization in cardiomyopathy.