Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Orexins induce increased excitability and synchronisation of rat sympathetic preganglionic neurones
Ist Teil von
The Journal of physiology, 2003-06, Vol.549 (3), p.809-821
Ort / Verlag
Oxford, UK: The Physiological Society
Erscheinungsjahr
2003
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
The neuropeptides orexin A and B are synthesised by perifornical and lateral hypothalamic (LH) neurones and exert a profound
influence on autonomic sympathetic processes. LH neurones project to spinal areas containing sympathetic preganglionic neurones
(SPNs) and therefore may directly modulate sympathetic output. In the present study we examined the possibility that orexinergic
inputs from the LH influence SPN activity. Orexin-positive neurones in the LH were labelled with pseudorabies virus injected
into the liver of parasympathetically denervated animals and orexin fibres were found adjacent to the soma and dendrites of
SPNs. Orexin A or B (10â1000 n m ) directly and reversibly depolarised SPNs in spinal cord slices. The response to orexin A was significantly reduced in the
presence of the orexin receptor 1 (OX1R) antagonist SB334867A at concentrations of 1â10 μ m . Single cell reverse transcriptase-polymerase chain reaction revealed expression of mRNA for both OX1R and OX2R in the majority
of orexin-sensitive SPNs. The orexin-induced depolarisation involved activation of pertussis toxin-sensitive G-proteins and
closure of a K + conductance via a protein kinase A (PKA)-dependent pathway that did not require an increase in intracellular Ca 2+ . Orexins also induced biphasic subthreshold membrane potential oscillations and synchronised activity between pairs of electrically
coupled SPNs. Coupling coefficients and estimated junctional conductances between SPNs were not altered indicating synchronisation
is due to activation of previously silent coupled neurones rather than modulation of gap junctions. These findings are consistent
with a direct excitation and synchronisation of SPNs by orexinergic neurones that in vivo could increase the frequency and coherence of sympathetic nerve discharges and mediate LH effects on sympathetic components
of energy homeostasis and cardiovascular control.