The epithelial sodium channel (ENaC) plays a crucial role in electrolyte homeostasis by mediating the transport of sodium ions across the apical membrane of epithelial cells. It is the only constitutively active member of the degenerin/ENaC protein family and is, consequently, stringently regulated. The canonical ENaC comprises three subunits (α, β and γ), but a fourth δ-subunit can replace α, forming functional δβγ-ENaCs which produce larger ion currents in heterologous expression systems (Wichmann et al. 2018). However, the physiological role of the δ-subunit is unknown, mainly since rats and mice – popular animal models in physiological research – lack a functional gene for this subunit. Therefore, in order to establish a suitable mammalian model in which the physiology of δ-ENaC could be investigated, Cavia porcellus (guinea pig) ENaC isoforms were heterologously expressed in Xenopus laevis oocytes and electrophysiologically characterized, using the Patch-Clamp technique. The specific aim of this project was to investigate whether enhanced ion currents generated by C. porcellus δβγ-ENaCs compared to αβγ-ENaCs are due to differences in single channel conductance. cRNAs coding for C. porcellus αβγ- and δβγ- ENaCs were diluted in RNAse-free water to a final concentration of 20 ng/μl per subunit. Xenopus ovary lobes were purchased from the European Xenopus Resource Centre (EXRC). Stage V/VI oocytes were isolated from at least 3 different Xenopus ovaries, injected with 32.2 nl of cRNA and were incubated at 16°C in a low-sodium culture oocyte Ringer’s solution (Wichmann et al. 2019). All procedures involving Xenopus ovaries and oocytes were approved by the Animal Welfare and Ethical Review Body of Newcastle University (project ID No: ID 630). Cell-attached Patch-Clamp recordings were performed on mechanically devitellinised oocytes 2-7 days after cRNA injection, as described by Wichmann et al. (2018). Current signals (pA) were obtained under different holding potentials (VM 0 to -100 mV). For each recording (n), single channel amplitudes of at least 3 events were measured and the slope conductance was determined by linear regression. Values presented are means ± standard error of mean (S.E.M) and were analysed for significance by Student’s unpaired t-test. There was no significant difference between the slope conductance (Gslope) of the two ENaC isoforms (t= 0.59, d.f.= 10, p= 0.571). Specifically, αβγ-ENaC had a Gslope of 4.27 ±1.42 pS (n=6) and δβγ-ENaC a Gslope of 4.05 ± 3.45 pS (n=6). In conclusion, there is no difference in the single channel conductance between C. porcellus αβγ- and δβγ-ENaCs. This suggests that channel open probability or membrane abundance likely account for increased transmembrane currents generated by δβγ-ENaCs compared to αβγ-ENaC in C. porcellus.