Dataset Information
TRPV4 and K(Ca) ion channels functionally couple as osmosensors in the paraventricular nucleus.
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ABSTRACT: Background and purpose
Transient receptor potential vanilloid type 4 (TRPV4) and calcium-activated potassium channels (KCa ) mediate osmosensing in many tissues. Both TRPV4 and KCa channels are found in the paraventricular nucleus (PVN) of the hypothalamus, an area critical for sympathetic control of cardiovascular and renal function. Here, we have investigated whether TRPV4 channels functionally couple to KCa channels to mediate osmosensing in PVN parvocellular neurones and have characterized, pharmacologically, the subtype of KCa channel involved.Experimental approach
We investigated osmosensing roles for TRPV4 and KCa channels in parvocellular PVN neurones using cell-attached and whole-cell electrophysiology in mouse brain slices and rat isolated PVN neurons. Intracellular Ca(2+) was recorded using Fura-2AM. The system was modelled in the NEURON simulation environment.Key results
Hypotonic saline reduced action current frequency in hypothalamic slices; a response mimicked by TRPV4 channel agonists 4?PDD (1??M) and GSK1016790A (100?nM), and blocked by inhibitors of either TRPV4 channels (RN1734 (5??M) and HC067047 (300?nM) or the low-conductance calcium-activated potassium (SK) channel (UCL-1684 30?nM); iberiotoxin and TRAM-34 had no effect. Our model was compatible with coupling between TRPV4 and KCa channels, predicting the presence of positive and negative feedback loops. These predictions were verified using isolated PVN neurons. Both hypotonic challenge and 4?PDD increased intracellular Ca(2+) and UCL-1684 reduced the action of hypotonic challenge.Conclusions and implications
There was functional coupling between TRPV4 and SK channels in parvocellular neurones. This mechanism contributes to osmosensing in the PVN and may provide a novel pharmacological target for the cardiovascular or renal systems.
SUBMITTER: Feetham CH
PROVIDER: S-EPMC4376454 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
Publications
TRPV4 and K(Ca) ion channels functionally couple as osmosensors in the paraventricular nucleus.
British journal of pharmacology 20150123 7
<h4>Background and purpose</h4>Transient receptor potential vanilloid type 4 (TRPV4) and calcium-activated potassium channels (KCa ) mediate osmosensing in many tissues. Both TRPV4 and KCa channels are found in the paraventricular nucleus (PVN) of the hypothalamus, an area critical for sympathetic control of cardiovascular and renal function. Here, we have investigated whether TRPV4 channels functionally couple to KCa channels to mediate osmosensing in PVN parvocellular neurones and have charact ...[more]
