Putative role of epithelial sodium channels (ENaC) in the afferent limb of cardio renal reflexes in rats.
Recent studies suggest a role of ion channels of the DEG/ENaC family for mechanosensation in different species and in baroreceptor reflex control in rats. We tested the hypothesis that ENaC within the cardiac sensory network are mandatory for mechanosensation. Experiments were performed in male Sprague-Dawley rats, isolated nodose ganglion cells with cardiac afferents and isolated vagus nerves. Epicardial delivery of the amiloride analogue benzamil intended to specifically inhibit ENaC presumably located on cardiac sensory afferents indeed blunted the mechanosensitive (i. e., sympathoinhibition by intravenous volume loading [-32% and -42% in treated groups vs. -67% in controls; n = 7 each; p < 0.05]) as well as-though to a lesser extent-the 5-HT(3)-mediated chemosensitive cardiorenal reflex in vivo in a dose-dependent manner. Using patch clamp technique, however, it turned out that neither amiloride nor benzamil influenced mechanically induced currents in ganglion nodosum cells in vitro, stimulated by hypoosmotic stress. The unspecific stretch activated ion channel blocker gadolinium completely abolished mechanically induced currents, indicating respective cells were mechanosensitive. In isolated vagus nerves benzamil impaired action potentials obtained by electrical stimulation (C-spike amplitude [-33%]; latency [+12%]; n = 8; p < 0.05). Our findings at least cast doubt on ENaC exclusively playing a specific role as mechanotransducers within the cardiac sensory network. Other ion channels might be involved. Furthermore the observed findings in vivo could also be due to unspecific disturbance of afferent signal conduction.
Ditting
Tilmann
T
Department of Nephrology, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany, Ditting@em.uni-frankfurt.de
Linz
Peter
P
Hilgers
Karl F
KF
Jung
Oliver
O
Geiger
Helmut
H
Veelken
Roland
R
D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D022062:Electrophysiologic Techniques, Cardiac; D004848:Epithelium / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009620:Nodose Ganglion / Q000166:cytology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D015222:Sodium Channels; C013407:benzamil; D000584:Amiloride