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Figures
Figure 1. Time-course of epithelial sodium channel (EnaC) expression in the Xenopus oocyte system. Oocytes were injected with rENaC αβγ (⧫), αβ (▵), αγ (⋄), βγ (○), or water and were measured by a two-electrode voltage clamp every day. In the upper panel, the maximal relative currents to the wild-type (WT) are expressed. At day 6, P < 0.05 for all the conditions over water-injected oocytes.
Figure 2. Splice variants of the α subunits leading to truncated proteins. A human splice-variant found in a pulmonary cell line (h αENaCx) results in an interrupted α subunit at the junction of exons III and IV. A splice-variant (h αENaC+Alu) amplified from pooled human cDNAs results in the insertion of an Alu cassette, leading to a frameshift and a putative truncated protein after exon VIII. Two splice-variants cloned from the rat taste bud (r αENaCa and b) lead to a truncation of the α subunit at the junction between exons VIII and IX, as a splice-variant of an α-like subunit identified in the chicken cochlea (cc αENaC).
Tables
Type Inheritance Clinical and Biochemical Characteristics Molecular Pathology OMIM a AR, autosomal recessive; AD, autosomal dominant; PAC, plasma aldosterone concentration; PRA, plasma renin activity. b Gordon syndrome or familial hyperkaliemic hypertension. c Transient PHA. I AR Renal: salt wasting, hyponatremia, hyperkalemia, metabolic acidosis elevated PAC and PRA, treatment by salt supplementation for life Mutations on the three genes coding for the epithelial sodium channel 264350 Lung: chest congestion, cough and tachypnea Na+ and Cl− elevated in sweat, saliva, and stool AD Renal: salt wasting, hyponatremia, hyperkalemia, metabolic acidosis, elevated PAC and PRA, treatment by salt supplementation Mutations on the gene coding for the mineralocorticoid receptor 177735 Spontaneous remission over time. IIb AD Hyperkalemia, hypertension, hyperchloremic acidosis, normal PAC, low PRA, treatment by thiazide diuretics At least three subtypes: subtype a: associated with locus on chromosome 1q31–q42 (gene unknown) 145260 subtype b: mutations on the gene coding for WNK4 601844 subtype c: mutations on the gene coding for WNK1 605232 IIIc No Hyperkalemia, acidosis, elevated PAC and PRA, low glomerular filtration rate. Secondary to: excessive salt loss: intestine, sweat nephropathies: obstructive uropathy, sickle cell and lead nephropathy, amyloidosis, urinary tract infections. Subunit Mutation Type Genotype Reference Clinical Description Reference a NR, not reported. α I68 frameshift Homozygous 106 156 C133Y Homozygous 54, 139 Lifton RP, personal communication S483 frameshift Homozygous 119 119 R492 stop Homozygous Bonny O, manuscript in preparation Bonny O, manuscript in preparation R508 stop Homozygous 106, 118 2,115,157 R56 stop and R139 deletion Compound heterozygous 118 NRa T168 frameshift and F435 frameshift Compound heterozygous 118 NR S243 frameshift and S483 frameshift Compound heterozygous 119 116 S562L and S483 frameshift Compound heterozygous 119 119 β G37S Homozygous 106 106 T216 frameshift and D305 frameshift Compound heterozygous 118 NR γ KYS106–108→N and 134stop Homozygous 131 130 V543 frameshift and acceptor splice site mutation exon 13 Compound heterozygous 153 153 Subunit Human Mutation Tested in the X. laevis Oocyte as Expression System % of the WTa Reference a WT, wild-type ENaC. α I68 frameshift Human αI68fr ratβ ratγ 0.1% 138 C133Y Rat αC158Yβγ 71% at 19°C 139 13% at 30°C R492 stop Human αR492*βγ 2% Bonny O, manuscript in preparation R508 stop Human αR508*βγ 8% 42 Rat αL535*βγ 13% S562L Rat S589Lβγ <0.1% Gautschi I, Schild L, Kellenberger S, personal communication β G37S Rat αβG37Sγ 50% 47, 106 Mutations % of the WT Activity in the Oocyte First Episode of PHA (d) Na+ (mmol/L) K+ (mmol/L) PAC (μg/L) Other Organs Involved than Kidney Reference a PAC, plasma aldosterone concentration; to translate μg/L in nmol/L, multiply by 2.771; normal range for neonates, 0.20 to 1.00 μg/L. WT, means wild-type; ND, not determined. αI68fr 0.1% 7 124 7.7 1.87 ND 106 αI68fr 0.1% 1 126 11.2 6.28 ND 106 αI68fr 0.1% 8 128 10.9 15.16 ND 106 αC133Y 13% 14 147 8.2 6.24 ND Lifton RP, personal communication αS483fr ND 9 116 10.4 11.91 yes, sweat glands and lung 119 αR492stop 2% 7 124 9.7 6.50 yes, sweat glands Bonny O, manuscript in preparation αR508stop 8% 9 125 10 14.32 yes, lung, salivary and sweat glands 106 αS243fr/αS483fr ND 5 124 10.4 11.15 Unknown 119 αS243fr/αS483fr ND 4 129 8.4 4.8 yes, sweat glands and lung 119 αS562L/αS483fr ND (<0.1% for S562L) 11 106 11.4 2.17 yes, sweat glands and lung 119 βG37S 50% 19 133 8.2 1.00 ND 106 γV543fr/splice site mutation ND 7 116 8.6 10.73 yes, lungs 153
Disturbances of Na/K Balance: Pseudohypoaldosteronism Revisited
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