Characterization of an Extensive Transverse Tubular Network in Sheep Atrial Myocytes and its Depletion in Heart Failure

Abstract

Background— In ventricular myocytes, the majority of structures that couple excitation to the systolic rise of Ca 2+ are located at the transverse tubular (t-tubule) membrane. In the failing ventricle, disorganization of t-tubules disrupts excitation contraction coupling. The t-tubule membrane is virtually absent in the atria of small mammals resulting in spatiotemporally distinct profiles of intracellular Ca 2+ release on stimulation in atrial and ventricular cells. The aims of this study were to determine (i) whether atrial myocytes from a large mammal (sheep) possess t-tubules, (ii) whether these are functionally important, and (iii) whether they are disrupted in heart failure. Methods and Results— Sheep left atrial myocytes were stained with di-4-ANEPPS. Nearly all control cells had an extensive t-tubule network resulting in each voxel in the cell being nearer to a membrane (sarcolemma or t-tubule) than would otherwise be the case. T-tubules decrease the distance of 50% of voxels from a membrane from 3.35�0.15 to 0.88�0.04 μm. During depolarization, intracellular Ca 2+ rises simultaneously at the cell periphery and center. In heart failure induced by rapid ventricular pacing, there was an almost complete loss of atrial t-tubules. The distance of 50% of voxels from a membrane increased to 2.04�0.08 μm, and there was a loss of early Ca 2+ release from the cell center. Conclusion— Sheep atrial myocytes possess a substantial t-tubule network that synchronizes the systolic Ca 2+ transient. In heart failure, this network is markedly disrupted. This may play an important role in changes of atrial function in heart failure.