Connexins and impulse propagation in the mouse heart

Connexins and Propagation, Gap junction channels are essential for normal c ardiac impulse propagation. Three gap junction proteins, known as connexins , are expressed in the heart: Cx40, Cx43, and Cx45, Each of these proteins forms channels with unique biophysical and electrophysiologic properties, a s well as spatial distribution of expression throughout the heart. However, the specific functional role of the individual connexins in normal and abn ormal propagation is unknown. The availability of genetically engineered mo use models, together with new developments in optical mapping technology, m akes it possible to integrate knowledge about molecular mechanisms of inter cellular communication and its regulation with our growing understanding of the microscopic and global dynamics of electrical impulse propagation duri ng normal and abnormal cardiac rhythms. This article reviews knowledge on t he mechanisms of cardiac impulse propagation, with particular focus on the role of cardiac connexins in electrical communication between cells. It sum marizes results of recent studies on the electrophysiologic consequences of defects in the functional expression of specific gap junction channels in mice lacking either the Cx43 or Cx40 gene. It also reviews data obtained in a transgenic mouse model in which cell loss and remodeling of gap junction distribution leads to increased susceptibility to arrhythmias and sudden c ardiac death. Overall, the results demonstrate that these are potentially p owerful strategies for studying fundamental mechanisms of cardiac electrica l activity and for testing the hypothesis that certain cardiac arrhythmias involve gap junction or other membrane channel dysfunction, These new appro aches, which permit one to manipulate electrical wave propagation at the mo lecular level, should provide new insight into the detailed mechanisms of i nitiation, maintenance, and termination of cardiac arrhythmias, and may lea d to more effective means to treat arrhythmias and prevent sudden cardiac d eath.