Molecular and immunochemical characterization of the ionotropic glutamate receptors in the rat heart

Abstract

Excitatory amino acids (EAA) and glutamate receptors (GluRs) play a fundamental role in the central nervous system (CNS). Ionotropic glutamate receptors (iGluRs) are coupled to ion channels, which are classified according to their most selective agonists. These ligand-gated channels are permeable to Na+, K+, and Ca+. Interaction of EAA receptor is linked to Ca+2/Na+ influx. Influx changes lead to an action potential, which in the heart is transmitted along the cardiocyte membrane. Furthermore, the heart has a rich innervation and specialized conduction system for rapid conduction and regulation of cardiac rhythmicity. Availability of EAA receptors in the heart might be important for cardiac function. The following GluRs were cloned by isoform-specific RT-PCR from rat heart ribonucleic acid (RNA): GluR 1, GluR 3, GluR 4, GIuR 7, Ka 1, and Ka 2. Expression in cardiac tissue was confirmed by western (for anti-GluR 2/3) and northern blots (for GluR 3, NMDAR 1, and Ka 2). The anatomical distribution was investigated by immunohistochemistry. Antibodies to GluR 2/3, GluR 5/6/7, Ka 2, and NMDAR 1 showed the strongest signals. These signals were specifically localized to cardiac nerve terminals, ganglia, conducting fibers, and some to myocardiocytes particularly in the atrium. Each antibody had a specific pattern of distribution. This anatomical localization suggests that they might play a role in cardiac electrophysiology and pathology.