Abnormal control of the sympathetic nervous system is a feature of heart failure. Sympathetic tone changes in response to cardiovascular demand monitored by visceral receptors sensitive to haemodynamic changes and blood oxygen levels. Atrial volume receptors (AVRs) at the venous atrial junction are mechanoreceptors which convey information to the CNS about venous volume. The details of how these receptors sense volume changes and transduce that change into a neural output have yet to be described. AVRs are typically classified as either A- or B-type according to their pattern of discharge. Broadly, A-type receptors respond to atrial contraction while B-type are stimulated by atrial filling and are considered to be volume receptors. However, intermediate AB-type discharges have also been described. The identification of mechanosensitive channels in vertebrates remains elusive. Two channel protein families in particular are candidates: the Epithelial Na Channel/Degenerin/Acid Sensing Ion Channel (ENaC/Degenerin/ASIC) and Transient Receptor Potential (TRP) families [1]. The g subunit of ENaC is expressed in baroreceptor nerve terminals innervating the aortic arch and carotid sinus in mice [2]. ASIC1, 2 and 3 were found in aortic baroreceptor neurones in the nodose ganglia and their terminals in the aortic arch [3]. We have shown that in rat heart the TRP channels TRPC1 and TRPV4 are expressed in sensory endings found in regions of cavo-atrial endocardium where AVRs are located. The TRPC1 and TRPV4-IR co-localises with extensive synaptophysin (SYN)-IR, a marker of synaptic-like vesicles (SLVs) common to many mechanosensory endings [4]. So far we have found no evidence of ENaC/DEG/ASIC-IR, suggesting the volume receptor may rely on different molecular components from those reported for the baroreceptor. Nevertheless the distinctive synaptophysin reactivity indicates possible commonalities with the model proposed by Bewick et al. [5] whereby the excitability of mechanosensory endings is regulated by mechanical activity which stimulates the recycling and release of a neuromodulator from SLVs. In a parallel study an in vitro preparation of rat vagus-cavo-atrium is being perfected by colleagues in Dublin. This permits direct recording and classification of atrial mechanoreceptors. This will confirm or refute the functional significance of proteins expressed in AVRs.