Immunocytochemical Localization of rH1 Sodium Channel in Adult Rat Heart Atria and Ventricle

BACKGROUND: Of the five sodium channel subtypes expressed in cardiac tissues, the rat (rH1) and human (hH1) isoforms are thought to be the predominant subtypes on the basis of heterologous expression studies. In this study, subtype-specific antibodies and immunocytochemistry were used to confirm protein expression and to localize rH1 protein in cardiac tissues. METHODS AND RESULTS: Subtype-specific antibodies immunolabeled adult rat heart tissue in a manner identical to that obtained with subtype-nonselective antibodies. All antibodies specifically bound to the surface and t-tubular systems of atrial and ventricular muscle cells. Cytoplasmic labeling, reflecting nascent sodium channels or cytoplasmic stores of sodium channel protein, was apparent. Most notably, all antibodies also specifically labeled the subset of intercalated disks located at the ends but not the sides of adjacent ventricular muscle cells. CONCLUSIONS: rH1 is the predominant subtype expressed on rat atrial and ventricular muscle cells. rH1 protein localization in surface and t-tubular membranes is consistent with its proposed role in coordinating membrane depolarization along the length and deep within cardiac muscle cells. rH1 protein localization in terminal intercalated disks suggests that sodium channels may also act as a localized voltage-dependent current amplifier, raising the safety margin for conduction; they also may contribute to anisotropic or saltatory conduction in cardiac tissues. These electrophysiological properties would be particularly important under conditions of altered, channel function resulting from ion channel gene defects (e.g., long QT syndrome), antiarrhythmic drug therapy, ischemia, or other heart diseases by influencing the electrophysiological substrate for ventricular tachyarrhythmias.