Introduction: In Olmsted syndrome of humans, a gain of function mutation of TRPV3 (hTRPV3) leads to severe hyperkeratosis of the skin (1). Recently, it has been suggested that the bovine analogue (bTRPV3) is involved in the uptake ofNH4+ (2,3). Data for the human analogue are lacking. Methods: Xenopus oocytes were injected with a linearized strep-tagged cRNA of hTRPV3, bTRPV3, or with RNAse-free water (control). The expression was verified using immunoblotting(n=8) and immunohistochemistry (n=3). Double barrelled pH-sensitive microelectrodes and the single channel patch clamp technique were used to investigate permeability to NH4+. Values are means ± S.E.M. (ANOVA on Ranks).Results: After switching from NMDGCl to NaCl solution, membrane potential depolarized in all groups (p≤0.005).Relative to NMDG+, permeability of Na+ was similar (p>0.4)in hTRPV3 (1.94 ± 0.17, n=16) and bTRPV3 (2.19 ± 0.18, n=18),both significantly (p0.5; hTRPV3: 7.57 ± 0.03, bTRPV3: 7.55 ± 0.05, control:7.62 ± 0.03). A switch to NH4Cl induced a significant depolarization(p≤0.001) and acidification (p≤0.001). The relative permeability of NH4+ versus NMDG+ was significantly higher(p=0.03) in bTRPV3 (3.81 ± 0.23) than in hTRPV3 (3.32 ± 0.28)or controls (3.09 ± 0.24). pHi was lower (p≤0.01) in hTRPV3(6.00 ± 0.11) than in bTRPV3 (6.33 ± 0.07) or controls(6.36 ± 0.09).In patch clamp experiments, large single channel conductances (>100 pS) for NH4+ were determined in over 50% of patches from both types of overexpressing oocytes (hTRPV3:178 ± 8 pS, n=15 of 25; bTRPV3: 158 ± 12 pS, n=11 of 20;p=0.13), but not in any patches from controls. Smaller channels(<100 pS) were observed in 62% of control (46 ± 9 pS),52% of hTRPV3 (63 ± 8 pS), and 35% of bTRPV3 patches(49 ± 11 pS). Interestingly, traces of eight hTRPV3 membrane patches simultaneously showed both large and small channels, not observed in bTRPV3. In 38% of control, 16% ofhTRPV3, and 10% of bTRPV3 patches, no channel activity was seen. In conjunction, overexpression of hTRPV3 or bTRPV3significantly enhanced single channel conductance (p≤0.005), while smaller endogenous conductances were suppressed. Conclusion: Both in the human and bovine species, an involvement of TRPV3 channels in the transport of NH4+ as a major product of protein metabolism appears likely. Given thatTRPV3 is highly expressed by keratinocytes (1,3), implications follow both for the pathophysiology of certain skin diseases in humans and for dietary uptake mechanisms across the ruminant forestomach. We further report that Xenopus oocytes express a high endogenous conductance for NH4+, requiring care when this expression system is chosen for studies of ammonia transport.