Synapses on NG2-expressing progenitors in the brain: multiple functions?

Progenitor cells expressing the proteoglycan NG2 represent approximately 5% of the total cells in the adult brain, and are found both in grey and white matter regions where they give rise to oligodendrocytes. The finding that these cells receive synaptic contacts from excitatory and inhibitory neurons has not only raised major interest in the possible roles of these synapses, but also stimulated further research on the developmental and cellular functions of NG2-expressing (NG2⁺) progenitors themselves in the context of neural circuit physiology. Here we review recent findings on the functional properties of the synapses on NG2⁺ cells in grey and white matter regions of the brain. In this review article we make an attempt to integrate current knowledge on the cellular and developmental properties of NG2⁺ progenitors with the functional attributes of their synapses, in order to understand the physiological relevance of neuron–NG2⁺ progenitor signal transmission. We propose that, although NG2⁺ progenitors receive synaptic contact in all brain regions where they are found, their synapses might have different developmental and functional roles, probably reflecting the distinct functions of NG2⁺ progenitors in the brain.     

Control of T-cell activation by CD4+ CD25+ suppressor T cells

Summary: Depletion of the minor (∼10%) subpopulation of CD4⁺ T cells that co-expresses CD25 (interleukin (IL)-2 receptor α-chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4⁺ T cells with anti-CD25 and complement results in the development of organ-specific autoimmunity. Autoimmune disease can be prevented by reconstitution of the animals with CD4⁺ CD25⁺ cells. CD4⁺ CD25⁺-mediated protection of autoimmune gastritis does not require the suppressor cytokines IL-4, IL-10, or transforming growth factor (TGF)-β. Mice that express a transgenic T-cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/K ATPase all develop severe autoimmune gastritis very early in life. CD4⁺ CD25⁺ T cells are also powerful suppressors of the activation of both CD4⁺ and CD8⁺ T cells in vitro . Suppression is mediated by a cell contact-dependent, cytokine-independent T–T interaction. Activation of CD4⁺ CD25⁺ via their TCR generates suppressor effector cells that are capable of non-specifically suppressing the activation of any CD4⁺ or CD8⁺ T cell. Activation of suppressor effector function is independent of co-stimulation mediated by CD28/CTLA-4 interactions with CD80/CD86. We propose that CD4⁺ CD25⁺ T cells recognize organ-specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4⁺ or CD8⁺ effector cells to suppress the development of autoimmune disease.     

A Study on Graft-versus-Host Reaction (GVHR) by Simonsen's Splenomegaly Assay Cells and Antigen Systems Involved in Induction of GVHR

Cells and histocompatibility antigen systems involved in graft-versus-host reactions (GVHR) were analyzed using Simonsen's splenomegaly assay employing various combinations of donor and F₁ hybrid recipients mice. Most of the cells proliferating in spleens of mice undergoing GVHR were J11d⁺, and had histological features of cells of the hematopoietic lineage. The proportions of CD3⁺ T cells were decreased in the spleens. Disparity at minor histocompatibility determinants of AKR, I-E and H-2D regions between B10.A(4R) donors and (4R × AKR) F₁ recipients evoked only negligible GVHR. On the contrary, disparity at H-2K and/or I-A regions appeared to be sufficient to permit induction of full GVHR. When surface markers of donor spleen cells were analyzed, it was shown that Thy-1⁺ and/or MEL-14⁺ cells caused a strong effect on GVHR. Further, either CD4⁺ or CD8⁺ T cell subset could induce significant GVHR. However, synergistic influences of these two T cell subsets on one another in GVHR were observed. The present results raise the possibility of using Simonsen's assay along with a number of reagents to identify the contribution of subsets of T lymphocytes and in analyzing precise contributions of cellular components from both donor and recipient, and also of the target antigen systems of the recipient that contribute to early events involved in GVHR.     

Peripheral T-cell Lymphomas Immunologic and Enzyme Histochemical Analysis of 15 Cases

Ffteen cases of peripheral T cell lymphoma were studied to evaluate the respective properties of various histologic types using enzyme histochemical and ultrastructural examinations in addition to immunological methods. Eleven cases in an ATLA negative group manifested various histologic patterns such as IBL like, pleomorphic and Lennert's lymphomas in comparison with the relatively monomorphic proliferation of neoplastic lymphoid cells in the 4 ATLA positive cases. The presence of neoplastic clear cells is characteristic of peripheral T-cell malignancies, and is likely to be found in CD4 lymphomas. There is an occasional reaction of epithelioid histiocytes and plasma cells with eosinophils, the former being designated Lennert's lymphoma and the latter IBL like T-cell lymphoma. Immunological examination revealed four immunophenotypic patterns: (1) CD2⁺3⁺4⁺8⁺, (2) CD2⁺ 3⁻4⁺8⁻, (3) CD2⁺3⁺4⁻8⁺, and (4) CD2⁺3⁺4⁺8⁺, but did not provide information concerning the intimate relationship between histologic types and immuno phenotyes. β-Glucuronidase reactivity, however, contributed to the distinction between helper and suppressor T cell malignancies, suggesting its usefulness for distinguishing these two cell types and their malignant counterparts.     

New variants of Ps salivary polymorphic proteins

Electrophoretic analysis of the Ps protein demonstrated the existence of phenotypes additional to those described by Azen & Denniston (1980). A hypothesis that the polymorphism of the Ps protein is determined by five expressed and one unexpressed alleles was supported by family studies. The gene frequencies in a Japanese population were Ps ^1F= 0.0016, Ps ¹= 0.2983, Ps ^2F= 0.0288, Ps ^2S= 0.0079, Ps ³= 0.0111, Ps ⁰= 0.6523.     

Subpopulations of T Lymphocytes in the Peripheral Blood, Dermal Lesions and Lymph Nodes of Post Kala-azar Dermal Leishmaniasis Patients

Distribution of different subpopulations of T cells in the dermal lesions, lymph nodes and peripheral blood of post kala-azar dermal leishmaniasis (PKADL) patients was studied by using appropriate phenotypic markers for CD2⁺, CD4⁺ and CD8⁺ cells. Histopathological studies of skin lesions showed marginal to massive infiltration of mononuclear cells depending upon the duration of illness and type of lesions. Thus, while the hypopigmented patches were represented by small focal collections of lymphocytes with scanty parasites in the dermis, these were replaced at the nodular stage with massive granulomas consisting of lymphocytes, plasma cells and histiocytes with numerous amastigotes. The involvement of CD4⁺ and CD8⁺ cell types in these lesions also showed a gradual change from the appearance of a few cells of both the phenotypes in early hypopigmented type to massive accumulation of cells, primarily of CD8⁺ phenotype, in the granuloma of nodular type. However, the observed preponderance of CD8⁺ cells at the lesion site of chronic PKADL patients is in contrast to their peripheral blood CD4⁺/CD8⁺ cell ratio (1.9:1) which remained within the normal limits. Similar studies of lymph nodes from PKADL patients with lymphadenopathy revealed infiltration of the cortical areas by T cells which were more of CD8⁺ than CD4⁺ phenotypes. All these results document the involvement of CD8⁺ cells in leishmanoid lesions. Thus, it is likely that these cells, in association with appropriate subpopulations of CD4⁺ cells, play a profound role in the evolution of dermal pathology in PKADL.     

Effects of gastrin on the histamine-secretory and proliferative activity of cultured carcinoid cells derived from the stomach of the rodent Mastomys natalensis

The effects of gastrin on the synthesis and release of hista-mine and on cellular prollferatlon were Investigated in a homotransplantable carcinold tumor implanted in the rodent Mastomys natalensis and in cultured cells derived from the tumor. The homotransplanted tumor was immunopositive for histamine, synaptophysin and protein gene product 9.5, and its cells contained numerous secretory granules that were vlsualized by electron microscopy. When carcinold cells were cultured in a medlum with a high concentration of gastrin-1 (10⁴ pg/mL) for 7 days, large electron-dense secretory granules were characteristically observed in the cytoplasm. By contrast, only a few such granules and numerous seaondary lysosomes were seen in cells that had been cultured in the same medium without gastrin-1. A high concentration of gastrin-1 (10⁴ pg/mL) slgniflcantly Increased the release of histamine Into the culture medium from the carcinoid cells compared wlth the control (P<0.05). Cellular proIiferation, as determlned by monitoring the incorporatlon of [methyl-³H]-thymidine into the carcinold cells Increased sig nfficantly at lower concentrations of gastrin-1 (10² and 10³ pg/ mL), (P<0.05). At higher concentratlons (10⁴ pg/mL or more), gastrin-1 had no effect on proliferatlon. These findings Indicate that gastrin stimulates the synthesis and release of histamlne by carclnoid cells, as well as their proliferation.     

Immunohistochemical characterization of thymic macrophages in normal and treated rats: a differential sensitivity to cyclosporine A

In the present study, a set of two monoclonal antibodies (TRPM1, TRPM2) was used to investigate the macrophage populations in the rat thymus and their different sensitivities to cyclosporine-A (CsA). With double immunohistochemical staining we demonstrated that, in the normal rat thymus, there are 3 populations of macrophages (TRPM1⁺, TRPM1/2⁺, TRPM2⁺), present in different proportions throughout the thymus. In the outer cortex TRPM1⁺ and TRPM1/2⁺ were present, but the TRPM1/2⁺ cells were more numerous. No TRPM2⁺ cells were observed in this area. The cortex and medulla showed all 3 types of cells with a majority of TRPM1/2⁺ cells. In the corticomedullary zone (CMZ) TRPM1/2⁺ and TRPM2⁺ macrophages were present in about equal proportion while only a few TRPM1⁺ cells were observed. After CsA treatment (for 21 days) profound changes occurred in the thymus; we observed a complete disappearance of the thymic medulla and a reduction in the total number of macrophages. The TRPM1⁺ macrophages had been eliminated, a few TRPM1/2⁺ cells were found while many of the cells were TRPM2⁺. The presence of the macrophages in different thymic areas suggests that they are a very heterogeneous population. The possible significance of the macrophage heterogeneity and the relationship to CsA sensitivity is discussed.     

Sequence variants in the 5' flanking region of the leptin gene are associated with obesity in women

Few mutations have been found in the human leptin gene and the relationship between leptin gene sequence variation and human overweight is uncertain. To determine whether sequence variation within the leptin gene and its regulatory elements contribute to extreme obesity, we screened ∼3 kb of the 5' flanking region and the three exons in 125 unrelated extremely obese (BMI ≥ 40 kg/m²) and 86 average weight women (BMI < 27 kg/m²). Within the protein coding regions only one heterozygous silent mutation was found (codon 102; AAC/AAT). Within the 5' flanking region, six frequent sequence variants were detected ( q > 0.10), and the allele frequencies of three of these variants differed between obese and average weight Caucasian women (+19, χ²= 4.46, p = 0.035; −1823, χ²= 4.36, p = 0.037; −2548, χ²= 5.73, p = 0.017). Nine infrequent sequence variants were detected ( q < 0.05) but they did not occur more often among obese women compared with those of average-weight. For extremely obese women, three polymorphisms (+19, −188, and −633) predicted the degree of obesity. Allelic variants may influence the regulation of the leptin gene and thereby influence body weight, particularly among extremely obese women. However, given the low variability in coding regions and the high variability in the 5' flanking region, discerning the functional significance of each variant is likely to be difficult.     

Determination of in vitro postantibiotic effects in Staphylococcus aureus and Escherichia coli by [3H]thymidine incorporation

Postantibiotic effects (PAE) and control-related effective regrowth time (CERT) of dicloxacillin, vancomycin, rifampin and gentamicin in Staphylococcus aureus and imipenem, gentamicin, tobramycin, doxycycline and rifampin in Escherichia coli were measured by standard viability counting and [³H]thymidine incorporation. For PAE determination, the two methods correlated well; r ² = 0.821 for S. aureus and r ² = 0.939 for E. coli . For viable counts below the detection limits of 10⁵ to 10⁶ log₁₀ CFU/mL, the PAE was overestimated by the [³H]thymidine method. Quantitation of CERT by both methods showed a good correlation, r ² = 0.867 for S. aureus and r ² = 0.997 for E. coli . Measuring [³H]thymidine incorporation in bacteria is a novel alternative method for the determination of PAE and CERT.     

Mitogenic Activation of Human Lymphocytes: a Protein A Plaque Assay Evaluation of Polyclonal B-Cell Activators

Using the protein A plaque assay, the capacity of various polyclonal B cell activators to induce differentiation in human B lymphocytes was investigated. Dextran sulphate and native Dextran were both virtually devoid of mitogenic properties, Lipopolysaccharide, however, was round to be a potent mitogen in human cells that, although giving rise to low DNA synthetic response, induced high numbers of immunoglobulin-synthesizing cells. Mean plaque-forming cell (PFC) numbers in healthy blood donors assayed on the optimal day (days 5–7) were 23, 493 IgM/10⁴ cells, 11, 288 IgG/10⁶ cells, and 2643 IgA/10⁶ cells. Values obtained in spleen cells, peaking at days 4–6, were slightly higher. Purified protein derivative (PPD) was equally or oven more-effective than lipopolysaccharide (LPS) in generating PFC of different subclasses in peripheral blood with mean of 29, 241 IgM/10⁶, 21, 269 IgG/10⁶, and 3681 IgA/10⁶. PPD furthermore induced a marked DNA synthetic response in human lymphocytes. These data suggest that LPS and PPD may both be used as functional markers in human cells when analysing patients with a suspected immunodeficiency state. It is suggested that cultures should be assayed using the protein A plaque assay, thereby being able not only to investigate the individual immunoglobulin classes but also to avoid the possible hazards involved in measuring antigen-specific responses in patients whose prior immunization to the antigen tested can never be totally excluded     

Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3+ Regulatory T cells

CD4⁺CD25⁺Foxp3⁺Regulatory T cells (Tregs) play important roles in regulating allergic inflammation. To analyse if allergen-DNA-modified dendritic cells (DC) can suppress allergic responses and what roles Treg cells play in DC-based allergen-specific immunotherapy. Immature DC were transfected with retrovirus encoding Der p2 DNA, and administered to mice that sensitized and challenged with Der p2 protein. After Treg cells were depleted with anti-CD25 mAb, mice were re-challenged to observe the airway inflammation, and Treg cells in spleen CD4⁺ T cells. And responses of spleen CD4⁺ T cells to Der p2 were determined. Co-culture of naïve CD4⁺ T cells with allergen-modified DC induced Foxp3+ Tregs. Sensitized and challenged mice developed allergic airway inflammation and Th2 responses, and decreased Foxp3⁺ Tregs. Treatment with allergen-modified-DC suppressed airway inflammation and Th2 responses, and increased IL-10 and IFN-γ production and Foxp3⁺ Tregs significantly; and eliminated the responses of CD4⁺ T cells to allergen. Administration of anit-CD25 mAb eliminated all the effects of modified-DC except for the increasing of IFN-γ. Allergen-modified DC can induce immune tolerance to allergens and reverse the established Th2 responses induced by allergen, with dependence on the induction of Foxp3⁺ Tregs.     

Effect of clindamycin in a model of acute murine toxoplasmosis

Objective: To characterize the antitoxoplasma activity of clindamycin in a murine model of acute toxoplasmosis.
Method: Rates of survival and mean survival times of Swiss Webster mice infected intraperitoneally with 10⁶-10² tachyzoites of the RH strain of Toxoplasma gondii treated with clindamycin or sulfamethoxazole (positive control) or untreated (negative control) were compared. Survivors were submitted to examination of untreated brain tissue preparations, intraperitoneal and peroral subinoculations of brain tissue homogenates into fresh mice, and to patho-histology, including immunohistochemistry, of brain and lungs.
Results: The effect of clindamycin treatment (400 mg/kg/day) on infected Swiss Webster mice was inoculum size dependent, ranging from no survivals in animals infected with 10⁶ parasites, to 100% survivals with an inoculum of 10². Treatment initiated 24 h before and at time of infection prolonged mean survival times comparably to sulfamethoxazole, and significantly when compared to untreated controls. In contrast, treatment initiated 48 h postinfection with an inoculum of 10⁶ did not postpone death. In the clindamycin-treated survivors, there was no biological or histologic evidence for the persistence of toxoplasma.
Conclusions: The results obtained show that at an appropriate parasite dose/drug dose ratio, clindamycin is strongly toxoplasmacidal in a murine model of acute toxoplasmosis.     

HIV Antigens and T-Cell Receptor Variable Beta Chain Families

The authors investigated whether the human immunodeficiency virus (HIV) has restrictive effects on the variable region of the β chain (Vβ) of the T-cell antigen receptor (TCR), by in vitro cultivation of non-HIV-infected peripheral blood lymphocytes with one of six HIV antigens or heat-inactivated whole virus (HIV-HI). Resting and blastic CD4⁺ and CD8⁺ cells were assessed with 3-colour cytofluorometry and monoclonal antibodies to various Vβ families/subfamilies. The Vβ families affected include V_β's 13.1/.3, 8, and 21 with gp120; V_β21 with gp160 and RT; V_β8 with p25; V_β's 8 and 21 with Rev; and V_β's 3 and 21 with HIV-2 Vpx. Vβ family-specific effects with HIV-HI did not differ significantly from those found with IL-2 stimulation. Findings differed between CD4⁺ and CD8⁺ cells. For CD4⁺ lymphocytes, significant Vβ-specific decreases were found, not the expansions found with superantigens or mitogens. CD8⁺ lymphocytes showed slight but significant expansions. The effects on V_β's 8, 13, and 21 are consistent with previous studies of HIV-infected persons. However, it is difficult to accept that antigens encoded by different HIV genetic regions cause proportionate diminutions of similar Vβ families. The authors suggest that these effects may be secondary to changes in cytokine profiles rather than direct interactions with TCR Vβ's.     

CD8+ Cells are the Main Producers of IL10 and IFNγ after Superantigen Stimulation

Purified CD8⁺ T cells were recently shown to produce TH1 as well as TH2 types of cytokines upon restimulation, indicating an important role for these cells in regulation of immune responses. However, it is not known if the CD8⁺ cells would contribute to cytokine production in the presence of cytokine secreting CD4⁺ cells. In the present study the authors have investigated the proportion of cytokine-producing CD4⁺ and CD8⁺ cells in the spleen after in vitro or in vivo stimulation. They found that stimulation of spleen cells with the superantigen Staphylococcal Enterotoxin B (SEB) in the presence of IL4 promoted production of IL10 and IFNγ predominately by CD8⁺ cells. In contrast, the production of IL4 was almost exclusively confined to the CD4⁺ subset. When priming with SEB in vivo before subsequent restimulation in vitro , a protocol previously shown to induce anergy, up to 80% of the IL10 and IFNγ positive cell expressed the CD8 marker. Taken together, these results emphasize the important role of cytokine-producing CD8⁺ cells and indicate that CD4⁺ and CD8⁺ T cells may, in a given situation, produce distinct cytokines.     

GLUCOCORTICOID-INDUCED GROWTH INHIBITION OF HUMAN NEOPLASTIC SALIVARY GLAND DUCT CELL LINE (HSG)

The purpose of this study was to examine the effect of glucocorticoid on human neoplastic salivary duct epithelial cell line (HSG). Dexamethasone was found to inhibit cell growth and to increase cell size and the ratio of protein content to DNA content in a cell. The inhibition of cell growth was dose-dependent; in comparison to the control (33.8±3.1 h), the population doubling time was 1.57-fold longer in 10⁵ M dexamethasone (P<0.01, N-K test). [³H] thymidine incorporation was inhibited in 45.5% of the control at 10^-5 M. Plating efficiency was 20.5±3.0% in 10⁵ M and 47.0±4.4% in the absence of dexamethasone. Cell diameters increased 1.29 fold in 10^-5 M dexamethasone in comparison to the control size (16.0±2.1 μm). The ratio of total protein content of DNA content increased 1.46 fold in 10^-5 M dexamethasone-treated cells on the seventh day of cultivation. Scatchard plot analysis using [6, 7-³H] -triamcinolone revealed that the HSG cells had apparent cytosolic glucocorticoid receptors with an equilibrium dissociation constant (Kd value) of 6.48 nM, whose number of binding sites (NBS) was 57.8fmol/mg protein.     

Family and population studies of SAHH and ADA polymorphisms. A possible pitfall in the ascertainment of SAHH electrophoretic phenotypes

Typing of both SAHH and ADA red cell electrophoretic patterns was carried out among the members of about 80 families from Latium (Central Italy) and in a random sample of about 350 individuals from two Italian regions, Latium and Sardinia.
1. The SAHH ¹ enzyme product provided another interesting example of a change in the electrophoretic pattern brought about by the haemolysate ageing. In vitro storage of SAHH 1 red cell lysates leads to the production of a pattern similar to that expected from a heterozygote SAHH 2–1. This change has been shown to be abolished by pretreating the sample with mercaptoethanol.
The results indicate that the systematic use of sulphydril reducing agents can provide a more reliable means of analysing the SAHH polymorphism if differently stored samples are to be compared by starch gel electrophoresis.
2. Evidence against complete linkage of the SAHH and ADA loci has been obtained from two informative SAHH/ADA matings encountered in this study.
3. The SAHH allele frequencies observed in the two samples analysed were: SAHH ¹= 0.969, SAHH ²= 0.024, SAHH ³= 0.007 (Latium) and SAHH ¹= 0.973, SAHH ²= 0.011, SAHH ³= 0.016 (Sardinia).
4. The ADA ² allele frequency estimates were: 0.083 (Latium) and 0.059 (Sardinia). These figures are almost identical to those already reported for the same two regions.     

Calcium buffering in rodent olfactory bulb granule cells and mitral cells

In the mammalian olfactory bulb, axonless granule cells (GCs) mediate self- and lateral inhibitory interactions between mitral cells (MCs) via reciprocal dendrodendritic synapses. Calcium signals in the GC dendrites and reciprocal spines appear to decay unusually slowly, hence GC calcium handling might contribute to the known asynchronous release at this synapse. By recording fluorescence transients of different Ca²⁺-sensitive dyes at variable concentrations evoked by backpropagating action potentials (APs) and saturating AP trains we extrapolated Ca²⁺ dynamics to conditions of zero added buffer for juvenile rat GC apical dendrites and spines and MC lateral dendrites. Resting [Ca²⁺] was at ∼50 n m in both GC dendrites and spines. The average endogenous GC buffer capacities (κ_E) were within a range of 80–90 in the dendrites and 110–140 in the spines. The extrusion rate (γ) was estimated as 570 s⁻¹ for dendrites and 870 s⁻¹ for spines and the decay time constant as ∼200 ms for both. Single-current-evoked APs resulted in a [Ca²⁺] elevation of ∼250 n m . Calcium handling in juvenile and adult mouse GCs appeared mostly similar. In MC lateral dendrites, we found AP-mediated [Ca²⁺] elevations of ∼130 n m with a similar decay to that in GC dendrites, while κ_E and γ were roughly 4-fold higher. In conclusion, the slow GC Ca²⁺ dynamics are due mostly to sluggish Ca²⁺ extrusion. Under physiological conditions this slow removal may well contribute to delayed release and also feed into other Ca²⁺-dependent mechanisms that foster asynchronous output from the reciprocal spine.     

The CD4+CD8+ and CD4+ Subsets of FOXP3+ Thymocytes Differ in their Response to Growth Factor Deprivation or Stimulation

The timing of thymic regulatory T (Treg) cell commitment remains unclear. Specifically, there is disagreement as to whether the CD4⁺CD8⁺ FOXP3⁺ thymocytes are precursors of mature CD4⁺ FOXP3⁺ Treg cells, or an independent Treg cell lineage. We reasoned that precursors should be more susceptible to apoptosis than mature Treg cells, and tested this by growth factor removal and anti-CD3 stimulation. Both treatments resulted in an increase of CD4⁺ FOXP3⁺ thymocytes, whereas the frequency of CD4⁺CD8⁺ FOXP3⁺ thymocytes decreased significantly. These changes were accompanied by an increase of annexin⁺ apoptotic cells. Both of these FOXP3⁺ subsets expressed higher levels of Bcl-2 and BIM than other thymocytes, and while in our setting expression of BIM seemed to predispose the cells to apoptosis, Bcl-2 had no apparent protective effect. These results indicate that CD4⁺CD8⁺ FOXP3⁺ thymocytes are more susceptible to apoptosis than mature CD4⁺ FOXP3⁺ Treg cells. This is consistent with the view that they are still immature and thus likely to represent a precursor population.     

KCNQ1 is the luminal K+ recycling channel during stimulation of gastric acid secretion

Parietal cell (PC) proton secretion via H⁺/K⁺-ATPase requires apical K⁺ recycling. A variety of K⁺ channels and transporters are expressed in the PC and the molecular nature of the apical K⁺ recycling channel is under debate. This study was undertaken to delineate the exact function of KCNQ1 channels in gastric acid secretion. Acid secretory rates and electrophysiological parameters were determined in gastric mucosae of 7- to 8-day-old KCNQ1^+/+, ^+/– and ^−/− mice. Parietal cell ultrastructure, abundance and gene expression levels were quantified. Glandular structure and PC abundance, and housekeeping gene expression did not differ between the KCNQ1^−/− and ^+/+ mucosae. Microvillar secretory membranes were intact, but basal acid secretion was absent and forskolin-stimulated acid output reduced by ∼90% in KCNQ1^−/− gastric mucosa. Application of a high K⁺ concentration to the luminal membrane restored normal acid secretory rates in the KCNQ1^−/− mucosa. The study demonstrates that the KCNQ1 channel provides K⁺ to the extracellular K⁺ binding site of the H⁺/K⁺-ATPase during acid secretion, and no other gastric K⁺ channel can substitute for this function.