Na+ Channel Activity in C×43‐Defident Myocytes. Introduction: Dynamic interplay between active and passive electrical properties of cardiac myocytes is based on interrelationships between various channels responsible for depolarizing and repolarizing ionic currents and intercellular conductances. Mice with targeted disruption of the connexin43 (C×43) gene have hearts completely devoid of C×43, the principal gap Junctional protein expressed in mammalian hearts. Methods and Results: To determine whether cardiac myocytes that develop in an abnormal environment of reduced intercellular coupling have altered active membrane properties, we studied whole cell action potentials, Na+ channel currents, and Na+ channel expression and distribution via immunoblotting and confocal immunofluorescence in neonatal ventricular myocytes isolated from C×43 wild‐type, heterozygous, and homozygous null hearts. Action potential morphology, peak Na+ current, activation and inactivation kinetics, and Na+ channel protein expression and distribution were not different among myocytes isolated from wild‐type, heterozygous, or null hearts. Active membrane properties and Na+ channel activity were completely normal in C×43‐deficient myocytes isolated from hearts that have been shown to exhibit markedly reduced C×43 expression, gap junction number, and epicardial conduction delay. Conclusion: Despite a genetic inability to produce C×43 and a developmental history that culminates in marked gross cardiac morphologic abnormalities, premature death, and myocardial inexcitability ex vivo, cardiac Na+ channel distribution and function appear to he normal in C×43 null hearts. Although intimate structural and functional interrelationships have been described between ion channels and gap junction channels, expression and function of Na+ channels is not affected by the absence of C×43.