Introduction Gap junctions (GJ) are low resistance intercellular pathways which play a major role in myocardial conduction and their remodelling is a key contributor to arrhythmogenic states. Rotigaptide has been shown to increase GJ coupling after ischaemic stress. However, the effect of rotigaptide in acidotic conditions is not well characterised. We hypothesised that rotigaptide can reverse GJ uncoupling and resultant decreases in conduction velocities (CV) brought about by a low pH in HL-1 mouse atrial myocytes.

Methods A subclone of HL-1 cells were seeded as a drop onto microlectrode arrays and were allowed to form a 2D monolayer. Baseline recordings were made at a physiological pH of 7.4 by pacing just above the intrinsic rate at a cycle length of 1000 ms for 10 s. The same preparations were subsequently incubated in media of pH7.0 for 15 min. Incremental doses of 5 nM of rotigaptide were then added up to a maximum of 100 nM (n=8). Recordings were taken until no further changes in conduction velocities were seen.

Results A reduction of pH resulted in conduction block in all but one preparation (8.3%±23.6% of baseline, p<0.0001) and subsequent addition of rotigaptide increased the CV (82.4%±7.8% of baseline, p<0.0001). The CV after addition of rotigaptide was not significantly different to that of the baseline (p>0.05). Activation maps were plotted and the direction of propagation was unchanged (p>0.05).

Conclusions Administration of rotigaptide resulted in the reversal of conduction block induced by acidosis without affecting the activation pattern in this atrial cell model. We suggest that acidosis in the absence of ischaemia is a sufficient insult to see an effect with rotigaptide. Therefore rotigaptide may be of use in the reversal of non-ischaemic conduction abnormalities. Further work is required to assess whether rotigaptide can also reverse conduction slowing in whole heart arrhythmogenic states.

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Abstract 117 Figure 1

(A) An activation map from stimulation at baseline pH 7.4. (B) An activation map from the same array after the cells had been subjected to a low pH then given rotigaptide. (C) Conduction velocities taken from microelectrode arrays at baseline, pH 7.0 and pH 7.0 + rotigaptide. ****p<0.0001.