Published Online
on July 29, 2009

A more recent version of this article appeared on September 1, 2009

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Original Article

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

Katharine M, Dibb¹; Jessica D. Clarke; Margaux A. Horn; Mark A. Richards; Helen K. Graham; David A.. Eisner and Andrew W. Trafford

University of Manchester, Manchester, United Kingdom

^* Corresponding author; email: andrew.w.trafford{at}manchester.ac.uk

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 Ca ²⁺ release on stimulation in atrial and ventricular cells. The aims of the present study were to determine; i) if atrial myocytes from a large mammal (sheep) possess t-tubules, ii) if these are functionally important and, iii) if 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 µm to 0.88±0.04 µm. During depolarisation intracellular Ca²⁺ ([Ca²⁺]_i) rises simultaneously at the cell periphery and centre. 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 centre.

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.

Key Words: atrium • calcium • cells • heart failure • t-tubule