Putative role of epithelial sodiumchannels (ENaC)in theafferent limb of cardio renal reflexes in rats

Abstract. Recent studies suggest a role of ion channels of theDEG/ENaC family for mechanosensation in different species and inbaroreceptor reex control in rats. We tested the hypothesisthat ENaC within the cardiac sensory network are mandatory formechanosensation. Experiments were performed in maleSprague-Dawley rats, isolated nodose ganglion cells with cardiacafferents and isolated vagus nerves.Epicardial delivery of the amiloride analogue benzamilintended to specifically inhibit ENaC presumably located oncardiac 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—the5-HT₃-mediated chemosensitive cardiorenalreex in vivo in a dose-dependent manner. Using patch clamptechnique, however, it turned out that neither amiloride norbenzamil inuenced mechanically induced currents in ganglionnodosum cells in vitro, stimulated by hypoosmotic stress. Theunspecific stretch activated ion channel blocker gadoliniumcompletely abolished mechanically induced currents, indicatingrespective cells were mechanosensitive. In isolated vagus nervesbenzamil impaired action potentials obtained by electricalstimulation (C-spike amplitude [–33%]; latency [+12%]; n = 8; p< 0.05).Our ndings at least cast doubt on ENaC exclusivelyplaying a specific role as mechanotransducers within the cardiacsensory network. Other ion channels might be involved.Furthermore the observed ndings in vivo could also be due tounspecific disturbance of afferent signal conduction.