Heart disease is the biggest killer in the UK. Elevated sympathetic activity plays a role in heart disease, possibly due to disturbed osmosensing. Body fluid osmolarity is kept within a narrow range (∼290-300mOsm) controlled by the hypothalamus[1]. Hypertonic challenge leads to an increase in heart rate, blood pressure and renal sympathetic activity[2]. The paraventricular nucleus (PVN) of the hypothalamus has been implicated as having a role in osmoregulation. Treatment with hypertonic solutions has been shown to increase excitatory post synaptic potentials (EPSPs) within parvocellular neurons[3] and early fos expression increases in the PVN during water deprivation, causing hypertonic challenge in rats[4]. The transient receptor potential vanilloid channel TRPV4 is a possible candidate for volume sensing within the PVN as it has this role in other tissues[5]. We modelled the action of TRPV4 in Neuron (University of Yale) to determine if activity of this channel is likely to account for any changes in action potential (AP) frequency. We investigated the mechanism of osmoregulation within the parvocellular PVN by recording action currents as an indicator of underlying AP frequency in mouse brain slices using cell-attached patch clamp electrophysiology. Results given as a normalised mean±SEM; significances assessed by paired t-test. Hypotonic challenge (280mOsm) decreased AP frequency from 1.0±0.1Hz to 0.2±0.1Hz (n=7;p<0.01). The role of TRPV4 was investigated using the agonist 4-α-phorbol12,13-didecanoate (1μM) which decreased AP frequency to 0.6±0.5Hz (n=6;p<0.05). Conversely, upon addition of the TRPV4 antagonist RN1734 (5μM) decreases in AP frequency during hypotonic challenge were not seen (0.6±0.1Hz) (n=6; p>0.05). Since activation of TRPV4 leads to an increase in intracellular Ca2+; we hypothesised activation of Ca2+-activated K+ channels may be responsible for the decreased APs seen during our experiments. In support of this hypothesis we found that the effects of hypotonic challenge on AP frequency did not occur when inhibiting SK channels using UCL-1684 (30nM) as AP frequency increased from 0.2±0.3Hz to 0.7±0.2Hz (n=4;p<0.01). These results suggest TRPV4 expressing neurones, along with those expressing SK channels, are involved in osmosensing within the PVN.