In heart failure (HF) impaired ventricular relaxation means the atrial component of ventricular filling becomes more important. However, the amplitude of the Ca2+ transient in the atria, which underlies contraction, is decreased in HF. We have shown that a decrease in atrial L-type Ca2+ current (ICa-L) in HF underlies the decrease in Ca2+ transient amplitude but the mechanism behind the decrease in ICa-L in HF is not fully understood. Since transverse (t)-tubules, the deep invaginations of the cell membrane on which ICa-L resides, are almost completely lost in HF we investigated if ICa-L expression is decreased in the HF atria. HF was induced in sheep by rapid ventricular pacing at 210 beats per minute for ~6 weeks. A pacing lead was implanted in the endocardial apex of the right ventricle using a minimally invasive transvenous approach under fluoroscopic guidance. Surgical plane anaesthesia was maintained under isoflurane (3-5%) mixed with of oxygen (4.5-6 L.min-1). HF progression was monitored via echocardiography. We have employed a transcriptomic based approach through RNA-sequencing and qPCR of atrial tissue in control and HF in order to determine the causes of reduced Ica-L in HF. RNA was isolated from time-matched control and HF tissue using a Trizol method and column-size isolation. Following quality control, samples (normalised to 1 µg), with an RNA integrity number of ≈8, were synthesised into a cDNA library by polyadenylation enrichment and sequenced on an Illumina HiSeq4000 at the Wellcome trust for Human Genetics, Oxford. Samples were pooled and run across three lanes at a length of 75 base pairs with paired-end reads. Subsequent BAM files were analysed through DESeq2 at QFAB. Despite T-tubules loss in HF no change in the LTCC pore forming unit, CACNA1C, was detected through RNA-Seq or qPCR. Secondly, the associated subunits that form the LTCC together with CACNA1C were investigated. Expressional changes (P<0.05) were detected in three subunits, CACNB1, CACNA2D1 and CACNG6, none of which would be expected to decrease ICa-L . Finally, external modulators of ICa-L were considered. Phosphodiesterases (PDEs) are known to modulate ICa-L through protein kinases A and G (PKA/G) and were identified as potential candidates via PANTHER. Six PDEs were found to change in HF; PDEs 3B,3A,8A,6D and 12 were upregulated whilst 1B is downregulated. Of these six PDE3B is thought the most likely to co-localise to the LTCC nanodomain at the cell membrane. Increased expression of PDE3B was confirmed by qPCR and thus may be responsible for the decrease in ICa-L in HF. In conclusion we show the decrease in atrial ICa-L in HF is not brought about by a decrease in mRNA encoding the channel subunits. Our data suggests alterations in ICa-L regulators such as PRKAR1A and an increase in PDEs may play a role in decreased ICa-L function and warrant further investigation.