No abstract

Triggered activity in cardiac muscle and intracellular Ca2+ have been linked in the past. However, today not only are there a number of cellular proteins that show clear Ca2+ dependence but also there are a number of arrhythmias whose mechanism appears to be linked to Ca2+-dependent processes. Thus we present a systematic review of the mechanisms of Ca2+ transport (forward excitation-contraction coupling) in the ventricular cell as well as what is known for other cardiac cell types. Second, we review the molecular nature of the proteins that are involved in this process as well as the functional consequences of both normal and abnormal Ca2+ cycling (e.g., Ca2+ waves). Finally, we review what we understand to be the role of Ca2+ cycling in various forms of arrhythmias, that is, those associated with inherited mutations and those that are acquired and resulting from reentrant excitation and/or abnormal impulse generation (e.g., triggered activity). Further solving the nature of these intricate and dynamic interactions promises to be an important area of research for a better recognition and understanding of the nature of Ca2+ and arrhythmias. Our solutions will provide a more complete understanding of the molecular basis for the targeted control of cellular calcium in the treatment and prevention of such.

Abstract-The epicardial border zone (EBZ) of canine infarcts has increased anisotropy because of transverse conduction slowing. It remains unknown whether changes in gap junctional conductance (G j ) accompany the increased anisotropy. Ventricular cell pairs were isolated from EBZ and normal hearts (NZ). Dual patch clamp was used to quantify G j . At a transjunctional voltage (V j ) of ϩ10 mV, side-to-side G j of EBZ pairs (9.2Ϯ3.4 nS, nϭ16) was reduced compared with NZ side-to-side G j (109.4Ϯ23.6 nS, nϭ14, PϽ0.001). Key Words: gap junction Ⅲ myocardial infarction Ⅲ arrhythmias A fter coronary occlusion, a border zone of myocytes survives on the epicardial surface of healing canine infarcts, the epicardial border zone (EBZ). 1,2 The EBZ is characterized by reduced conduction velocity and increased anisotropy 1,2 associated with the occurrence of reentrant circuits and ventricular tachycardia. 1 Reduced sodium current 3,4 in EBZ myocytes may contribute to decreased conduction velocity. We studied gap junctional conductance in pairs of EBZ myocytes to determine if alterations occur and, therefore, might also contribute to changes in conduction and anisotropy. Connexin43 (Cx43) was quantified to determine if conductance changes were related to alterations in quantity of this gap junctional protein. Materials and Methods Preparation of Myocyte PairsCell pairs were obtained from EBZ of infarcted canine left ventricle, 5 days after coronary occlusion. Surgical methods for occlusion 1,2 and enzymatic techniques for cell disaggregation 4 have been described. EBZ tissue was removed from a region between the LAD and first circumflex branch that was visibly identified as infarct by its pale appearance (Figure 1), similar to the region sampled in previous studies of EBZ cells. 3,4 Because tachycardia was not induced nor reentry mapped, tissues did not come specifically from the central common pathway of reentrant circuits where we previously described redistribution of Cx43 gap junctions 5 (Figure 1). For normal pairs (NZ), tissue from a similar region in noninfarcted hearts was used.Studies were performed on both end-to-end-and side-to-sidecoupled EBZ and NZ myocyte pairs, 2 to 8 hours after isolation. The morphological criterion for side-to-side coupling was greater than 50% contact of cell lengths. The criterion for end-to-end coupling was contact of more than 60% of the end-to-end surfaces between each of two paired cells and less than 10% contact of side-to-side cell surfaces. 6 According to these criteria, about 60% of all cell pairs isolated were end-to-end coupled, and 40% were side-to-side coupled. End-to-end coupled pairs were easily identified under the optical microscope, because intercalated disks between the two cells could be seen clearly. It was sometimes difficult to identify a side-to-side coupled pair under the microscope because, on occasion, either a single large myocyte, or three myocytes coupled with each other without clear borders, resembled a cell pair. To verify that currents were recorded from a...