Connexins are well known to form intercellular channels, so-called gap junctions, which connect cells chemically and electrically. In the healthy heart, gap junctions between cardiomyocytes are usually formed by connexin 43 (Cx43). Six of these Cx43 proteins, located at the intercalated discs, form so-called hemichannels that connect to hemichannels of adjacent myocytes. Given their central role in electrical impulse propagation throughout the myocardium, alterations in gap junction activity likely contributes to the pathophysiology of ventricular and atrial arrhythmias. 1, 2

Nevertheless, in the sarcolemma of cardiomyocytes, connexins may also form orphaned hemichannels which do not couple with hemichannels of adjacent cells. In contrast to gap junctions, these connexin hemichannels are closed under resting conditions. Their opening, which has been studied mainly in isolated ventricular cardiomyocytes and expression systems, occurs primarily at positive membrane potentials in response to metabolic inhibition, low extracellular Ca2+ or an increase in intracellular Ca2+ concentration. 3