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Mechanistic insights into osmosensing in the PVN (1182.2)
Author(s) -
Feetham Claire,
BarrettJolley Richard
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1182.2
Subject(s) - trpv4 , transient receptor potential channel , membrane potential , reversal potential , biophysics , chemistry , electrophysiology , population , medicine , depolarization , patch clamp , agonist , endocrinology , ion channel , biology , receptor , environmental health
Cardiovascular disease is linked to disturbed osmosensing; effecting sympathetic activity, blood pressure and heart rate. The hypothalamus maintains plasma osmolality within a narrow range. The mechanisms are so far unknown; the paraventricular nucleus (PVN) may play a role. The transient receptor potential channel (TRPV4) and calcium activated potassium channels (K Ca ) are possible candidates for osmosensing. Having previously shown coupling of these channels in PVN neuron regulation in response to osmotic challenge, we wanted to further investigate the mechanisms responsible. Using cell‐attached patch clamp electrophysiology a population of ion channels were identified with a mean slope unitary conductance of 57±7pS and reversal potential of ‐5±3mV ( n=6 ). The channel had a mean open probability ( P o ) of 0.1±0.0 at ‐40mV; increased by 48±9% ( n=4 ) with the TRPV4 agonist 4αPDD. In isolated cells a resting membrane potential of ‐54±5mV and capacitance of 31±2pS were seen and a depolarisation of 11±2mV observed with 4αPDD ( n=4;p<0.05 ). To investigate intracellular [Ca 2+ ] by activation of TRPV4, [Ca 2+ ] was measured using Fura‐2AM. 4αPDD caused a significant transient increase of 45±12nM ( n=6;p<0.005 ). We have uncovered a potential mechanism for osmosensing within the PVN involving TRPV4 and K Ca coupling. Targeting these ion channels may provide novel therapies for cardiovascular disease.