Characterization of an extensive transverse tubular network in sheep atrial myocytes and its depletion in heart failure

Background-In ventricular myocytes, the majority of structures that couple excitation to the systolic rise of Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ release from the cell center. Conclusion-Sheep atrial myocytes possess a substantial t-tubule network that synchronizes the systolic Ca2+ transient. In heart failure, this network is markedly disrupted. This may play an important role in changes of atrial function in heart failure. © 2009 American Heart Association, Inc.