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Biomedical subjects

Y Zhou

Publications and source records attributed to Y Zhou.

At least 703 records · Page 39Linked to original sources
PubMed1996

Detection and enrichment of carcinoma-in-situ cells in semen by an immunomagnetic method using monoclonal antibody M2A.

Carcinoma-in-situ (CIS) is a precursor of germ cell cancers in the testis. Early detection and treatment of CIS can prevent the development of invasive cancer. We have developed an immunomagnetic approach for enrichment of CIS cells from semen. Immunomagnetic beads were coated with monoclonal antibody (mAb) M2A, which is specific for seminoma and CIS. In preliminary mixing experiments, cultured human HEY cells, which express the M2A surface antigen, were added to semen samples and recovered selectively by incubation with M2A-coated immunomagnetic beads followed by magnetic activated cell sorting (MACS). Application of this procedure to ejaculates from five subjects with CIS and 22 control subjects with no evidence of testicular neoplasia resulted in the preferential recovery of a population of large round cells from a 0.5 ml semen sample obtained from CIS subjects (median 1 x 10(4), range 2 x 10(3) to 2 x 10(4)) relative to controls (median 2 x 10(2); range 0 to 10(3)), with no overlap between the two groups (p < 0.001). These results suggest that a subpopulation of large round cells recovered from the semen of CIS patients by incubation with M2A-coated immunomagnetic beads and MACS are CIS cells. Immunomagnetic enrichment of CIS cells in semen will facilitate the definitive identification of exfoliated CIS cells in ejaculates and could be an important first step in a non-invasive screening procedure for testicular CIS.

Antibodies, Monoclonal↗
PubMed1996

In vivo inhibition of hepatitis B viral gene expression by antisense phosphorothioate oligodeoxynucleotides in athymic nude mice.

Antisense oligodeoxynucleotides strategies have been used both to study normal gene function and to block gene expression therapeutically. We have previously shown that a number of antisense oligonucleotides against hepatitis B virus (HBV) mRNA are able to inhibit viral gene expression in vitro. Here we report the establishment of an animal model producing HBV markers in athymic nude mice and inhibition of HBV gene expression and replication by antisense DNA in vivo. 2.2.15 cells (Hep-G2 cell line transfected with HBV genomes) were injected subcutaneously (s.c.) into athymic BALB/c nude mice at a total cell number of 0.5-1 x 10(8) per mouse. Transplanted tumours developed about 2 weeks after inoculation. Hepatitis B surface and e antigens (HBsAg and HBeAg), as well as HBV DNA, could be detected in the circulation of tumour-bearing mice. Hepatitis B surface antigen and hepatitis B core antigen (HBcAg) were demonstrated in tumour cells. After 10 days of tumour growth, antisense phosphorothioate oligonucleotide, complementary to the cap site of the SP II promoter of HBV mRNA, were injected by infiltration into or around the tumour as a daily dose of 20 micrograms per gram body weight. Treatment for a total of 10 days resulted in an effective inhibition of viral replication and gene expression. These results suggest therapeutic potential for antisense oligomers in the treatment of patients who are chronically infected with HBV.

Animals↗
PubMed1996

Stimulation of human lymphocyte proliferation and CD40 antigen expression by phosphorothioate oligonucleotides complementary to hepatitis B virus genome.

We have studied the proliferation and CD40 antigen expression of lymphocytes, and the cytotoxicity to monocytes, of antisense phosphorothioate oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA (sequence I) and the X gene (sequence II) in patients with chronic hepatitis B. The oligo sequence I stimulated proliferation of both T and, to a lesser extent, B cells. The percentage of cells expressing CD40 in T and B cell co-cultures increased from 4.2% to 13.8% after oligo stimulation in patients, while it increased form 4.7% to 48.6% in healthy controls. The sense sequence (sequence III) of the X gene also enhanced the expression of CD40 antigen in patients with hepatitis B. The proportion of CD40 cells (26%) in a resting B-cell preparation from hepatitis B patients decreased to zero after a 5-day culture with sequence I, but IgG levels in the culture supernatant increased. The cytotoxic properties of monocytes were not influenced by the oligos. These findings indicate that antisense oligos against hepatitis B virus (HBV) have mitogenic effects on the proliferation of human lymphocytes in a non-specific manner and may activate T cells to express CD40 antigen.

Adult↗
PubMed1996

Effects of UVB irradiation on keratinocyte growth factor (KGF) and receptor (KGFR) expression in cultured human keratinocytes.

Keratinocyte growth factor (KGF) and its receptor (KGFR) are thought to play important roles in normal keratinocyte growth and differentiation. Since UVB radiation is known to influence keratinocyte growth, we sought to determine whether UVB would alter the expression of KGF and KGFR. Using a reverse-transcription coupled polymerase chain reaction (RT-PCR), the present study examined the expression of KGF and KGFR mRNA in cultured normal human keratinocytes exposed to UVB irradiation. Total cellular RNA was extracted from cultured keratinocytes at various time points after irradiation, reverse transcribed and used for PCR amplification using primers specific for KGF and KGFR. Constitutive expression of KGFR mRNA, but not KGF mRNA, was detected in normal cultured human keratinocytes. After UVB irradiation at 300 J/m2, the KGF mRNA remained undetectable while the KGFR mRNA level was significantly decreased. The down-regulation of KGFR mRNA expression was also confirmed by Northern blot analysis. Immunohistochemical studies demonstrated a decreased positive signal of KGFR in human keratinocytes after UVB irradiation. Our results suggest a possible role for the KGF-KGFR signalling pathway in the skin after exposure to UVB, and that UVB-induced growth inhibition of keratinocytes in hyperproliferative skin disorders may be related to downregulation of KGFR.

Cells, Cultured↗
PubMed1996

Infection of primary human fetal astrocytes by human herpesvirus 6.

Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus which productively infects human CD4+ T cells and monocytes. HHV-6 is the etiologic agent for exanthem subitum (roseola), and it is well-known that central nervous system complications occur frequently during the course of HHV-6-associated disease. In addition, HHV-6 has been associated with encephalitis or encephalopathy. However, very little is known about its tropism for neural cells. There are reports that HHV-6 may infect some glial cell lines, but whether it can infect any primary neural cells is not known. Our studies show that both HHV-6A (GS) and HHV-6B (Z-29) can infect highly purified primary fetal astrocytes in vitro. Infected cells showed cytopathic effects, forming giant syncytia. In dual immunofluorescence assays, the infected cells were detected by antibodies against the HHV-6 p41 nuclear antigen and glial fibrillary acidic protein, indicating that the infected cells are indeed astrocytes. PCR and Northern (RNA) blot analyses also confirmed that the astrocytes are infected by HHV-6. The progeny virus did not alter its host range and could reinfect T cells as well as primary astrocytes. These findings suggest that infection of primary human astrocytes may play a role in the neuropathogenesis of HHV-6.

Astrocytes↗
PubMed1996

Longitudinal studies of viral sequence, viral phenotype, and immunologic parameters of human immunodeficiency virus type 1 infection in perinatally infected twins with discordant disease courses.

Perinatal human immunodeficiency virus type 1 (HIV-1) infections cause a broad spectrum of clinical disease and are variable in both the age of the patient at onset of serious disease and the progression of the clinical course. Heterozygotic perinatally infected twins with a marked difference in their clinical courses were monitored during the first 2 years of life. Twin B, the second-born twin, developed AIDS by 6 months of age and died at 22 months of age, while twin A remained minimally symptomatic through the first 2 years. Sequential blood specimens were obtained from the twins in order to characterize the immunologic properties of the children and the phenotypes and genotypes of the HIV-1 isolates at various times. Twin A developed neutralizing antibodies and a high-level antibody-mediated cellular cytotoxicity (ADCC) response, while twin B had no neutralizing antibody and a much lower ADCC response. The virus isolates obtained from the two children at various time points proliferated equally well in peripheral blood mononuclear cells, were nonsyncytium inducing, and could not infect established T-cell lines. They differed in their ability to infect primary macrophages. In parallel to the biological studies, the HIV-1 tat and part of the env gene sequences of the longitudinal isolates at four time points were determined. Sequences of virus from both twins at different time points were highly conserved; the viruses evolved at a similar rate until the last analyzed time point, at which there was a dramatic increase in sequence diversity for the sicker child, especially in the tat gene. Our results show that the viruses isolated at different times do not have significant changes in growth properties. The absence or low levels of neutralizing antibodies may correlate with disease progression in the twins.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Occupational and Environmental Risk Factors for Asthma in Rural Communities in China.

Respiratory allergens such as dust, gases/fumes, and hay smoke, which are frequently present in agricultural settings, can cause or aggravate asthma. The purpose of this study was to examine the relationships between occupational and environmental exposures and asthma in Chinese rural communities. The study population consisted of 28,946 people 15 years old or older, living in rural areas of Anhui province, China. A modified Mandarin translation of the ATS-DLD questionnaire was administered by trained interviewers to request information about exposures to specific occupational/environmental agents and respiratory disorders. In Huaining, the prevalence of wheezing was 3.8% for men; 2.1% for women; the prevalence of asthma was 1.6% for men; 1.8% for women. In Zongyang, the prevalence of wheezing was 2.7% for men; 1.9% for women; the prevalence of asthma was 1.7% for men; 1.2% for women. With control for potential confounders such as gender, age, residential area, education level, and smoking status, the pooled adjusted odds ratios (ORs) of wheezing and asthma for the group exposed to wood/hay smoke were 1.36 (95% CI: 1.14-1.61) and 1.27 (95% CI: 1.02-1.58), respectively. For coal-stove users, the pooled adjusted ORs were 1.47 (95% CI: 1.09-1.98) for wheezing and 1.51 (95% CI: 1.05-2.17) for asthma. After stratification of the subjects by dust type, the estimated ORs for wheezing were 1.58 (95% CI: 1.02-2.44) among the group exposed to inorganic dust and 3.03 (95% CI: 1.25-7.33) among the group exposed to metal dust. Asthma was not shown to be significantly associated with any specific dust type. Findings of the present study are consistent with previously reported adverse respiratory health effects related to occupational/environmental exposures to wood/hay smoke and dust, and indicate the need for further occupational disease surveillance in rural communities.

Journal Article↗
PubMed1996

Retinoic acid regulates insulin-like growth factor-binding protein expression in human osteoblast cells.

Retinoic acid (RA) regulates the growth and differentiation of numerous cells types and plays a key role in skeletal development. Previous studies have demonstrated that insulin-like growth factors (IGFs) are important local regulators of bone cell proliferation and differentiation and that IGF-binding proteins (IGFBPs) modulate their activities. In an attempt to test the hypothesis that RA mediates its effects on bone cells in part by regulating IGFBP expression, we first examined the effect of RA on IGFBP expression in human osteoblast model systems and then compared these responses to the effects of RA on IGFBP expression in human skin fibroblasts. The most dramatic effect of RA on IGFBPs++ in all cell types tested was to increase IGFBP-6 messenger RNA (mRNA) abundance more than 1000% of the control value. Significant effects on IGFBP-5 mRNA abundance were also found, with maximal reductions to 35% of control within 24 h of treatment. In addition, RNA maximally increased IGFBP-3 and -4 mRNA to 580% and 390% of the control value, respectively, in SaOS-2 cells, but had variable effects on IGFBP-3 and -4 mRNA levels in human bone cells, U2-OS, and human skin fibroblasts. The levels of the 24-, 29- to 32-, and 38- to 42 kDa IGFBPs in the conditioned medium of RA-treated cultures increased, as determined by ligand blot analysis, whereas the amount of IGFBP-5 was reduced, as determined by RIA. Cycloheximide abolished the RA-stimulated increase in IGFBP-6 mRNA and reduced baseline IGFBP-5 mRNA levels, but did not affect RA-modulated mRNA levels of the other IGFBPs. RA modestly increased the stabilities of all four IGFBP mRNAs, which could contribute to the observed increases in IGFBP-3 and IGFBP-4 mRNA levels; however, the 217% increase in the IGFBP-5 mRNA half- life in the presence of RA could not contribute to the reduction in mRNA levels. In addition, the small increase in the IGFBP-6 mRNA half-life could not account for the 1900% increase in the mRNA level. These data suggest that RA stimulated changes in IGFBP-5 and -6 mRNA levels may in part be mediated by alterations in transcription or other early posttranscription regulatory mechanisms. In conclusion, RA significantly regulates IGFBP expression in human osteoblast cells.

Cells, Cultured↗
PubMed1996

Estrogen rapidly induces the phosphorylation of the cAMP response element binding protein in rat brain.

Estrogen treatment of ovariectomized rats rapidly increases immunoreactivity for the phosphorylated form of the cAMP response element binding protein (CREB)in neurons of the preoptic area and the bed nucleus of the stria terminalis. These effects were detected within 15 minutes after estrogen exposure. Since the antisera used for these studies detect CREB phosphorylation at ser133, which is important for transcriptional activation these data provide a possible explanation for estrogen's effects on neuronal genes lacking estrogen response elements (EREs) but which contain cAMP response elements (CREs). These data also provide evidence for non-genomic effects of steroid hormones involving protein kinase associated signal transduction pathways traditionally associated with effects at the cell membrane.

Animals↗
PubMed1996

Dexamethasone stimulation of rat insulin-like growth factor binding protein-1 promoter activity involves multiple cis-elements.

Insulin-like growth factor binding protein-1 (IGFBP-1) modulates the mitogenic actions of IGF-I and IGF-II. Dexamethasone increases IGFBP-1 mRNA abundance and gene transcription in rat liver and in H4-II-E rat hepatoma cells. A glucocorticoid response element (GRE) located at nucleotide (nt) -91/-77 is required for dexamethasone to stimulate rat IGFBP-1 promoter activity in transient transfection assays in H4-II-E cells. Mutagenesis of nt -108/-99 (the M4 region of the insulin response element), however, decreased dexamethasone-stimulated promoter activity despite the presence of an intact GRE, suggesting that regulatory sites in addition to the GRE were required for optimal dexamethasone stimulation. To identify these sites, we introduced 5'-deletion and substitution mutations into rat IGFBP-1 promoter fragments coupled to a luciferase reporter gene and transfected these constructs into H4-II-E cells. Three sites are required for optimal basal promoter activity: a site (nt -62/-50) that binds the liver-enriched transcription factor, hepatocyte nuclear factor-1 (HNF-1), the M4 site, and a putative binding site for transcription factor AP-2 (nt -293/-286). The HNF-1 and M4 sites and an upstream site (nt -252/-236) are also involved in dexamethasone stimulation under some, but not all, circumstances. Mutation of either the HNF-1 site or the M4 site decreased dexamethasone stimulation by more than 80% in constructs whose 5'-end was at nt -92, -135, or -235 but not if the 5' -end was at nt -278 or -327. These results suggest that the nt -278/-236 region can compensate for the loss of the HNF-1 site or the M4 site but that the HNF-1 and M4 sites do not compensate for each other in constructs whose 5'-end was at nt -135 or -235, which lack the nt -278/-236 region. The site within the nt -278/-236 region was localized to nt -252/-236 by deoxyribonuclease I protection and transfection assays. Thus, several cis-elements in the rat IGFBP-1 promoter cooperate, in varying combinations, with the low-affinity GRE to allow optimal dexamethasone-stimulated promoter activity.

Animals↗
PubMed1996

Localization of Xcat-2 RNA, a putative germ plasm component, to the mitochondrial cloud in Xenopus stage I oocytes.

The mitochondrial cloud is a unique cell structure found in stage I Xenopus oocytes that plays a role in mitochondriogenesis and in the distribution of germ plasm to the vegetal pole. Xcat-2 RNA specifically localizes to the mitochondrial cloud and moves with it to the vegetal subcortex in stage II oocytes. Later, in the 4-cell embryo, it is found in a pattern identical to the germ plasm. Following microinjection into stage I oocytes, synthetic Xcat-2 RNAs localize to the mitochondrial cloud within 22 hours. Transcripts are stable over this time period with very little evidence of degradation. The Xcat-2 3'untranslated region was found to be both required and sufficient for mitochondrial cloud localization. Further deletion analysis narrowed this localization signal to a 250 nucleotide region at the proximal end of the 3'untranslated region. This region is different from, but overlaps with, a domain previously shown to be sufficient to direct Xcat-2 to the vegetal cortex in stage IV oocytes. Examination of early stage I oocytes reveals a time when Xcat-2 is uniformly distributed, arguing against vectorial nuclear export into the mitochondrial cloud. Analysis of localization at different time points does not suggest active transport to the mitochondrial cloud. We postulate that localization occurs by selective entrapment of Xcat-2 within the cloud by localized binding sites.

Animals↗
PubMed1996

Responsiveness of rat nonparenchymal liver cells and spleen cells to the decomposition of erythrocytes exposed to di-n-butyl phthalate and its metabolite.

We have reported that di-n-butyl phthalate (DBP) caused the depletion of circulating iron, characterized by the release of iron from both haemoglobin (Hb) and transferrin (Tf). The present study investigated whether the erythrocytes from DBP-treated rats were destroyed by nonparenchymal liver cells (NPC, including Kupffer cells) or spleen cells (SC). In the in vivo study, there were observed depletions of Hb in the blood and of iron in the hepatic Tf fraction, as well as an accumulation of iron in the hepatic hemosiderin (Hs) and splenic Tf fractions. In the in vitro study, mono-butyl phthalate (MBP), a metabolite of DBP, caused a depletion of iron in the plasma Tf, although a direct release of iron from Tf was not detectable. When erythrocytes from DBP-treated rats and erythrocytes preincubated with MBP both were incubated with NPC, respectively, the Hb was decomposed and the iron also accumulated in the cell debris. However, when the two kinds of erythrocytes were incubated with SC, respectively, no decomposition of Hb was observed at low and medium doses, but the highest dose induced an accumulation of iron to Tf. Therefore, the NPC may contribute in part to the decomposition of DBP- or MBP-affected erythrocytes.

Animals↗
PubMed1996

The natriuretic actions of vasopressin in the female rat: variations during the 4 days of the oestrous cycle.

The renal actions of vasopressin were studied in the conscious female rat. Vasopressin caused a dose-dependent increase in sodium excretion when administered at 40-160 pmol/min. The highest dose, which increased sodium excretion from 10.4 +/- 0.3 mumol/min (n = 32) to 18.3 +/- 0.8 mumol/min (n = 8, P < 0.001), also caused a significant rise in glomerular filtration rate (GFR). The antidiuretic and natriuretic responses to vasopressin varied significantly over the 4 days of the oestrous cycle. Both responses were greatest on pro-oestrus, being -57 +/- 3 and 52 +/- 3% above the control values with 80 pmol vasopressin/min. Responses of similar magnitude were also seen on dioestrus day 1. On these two cycle days the effects on urine flow and sodium excretion were accompanied by a significant increase in GFR. Smaller antidiuretic and natriuretic responses were seen on oestrus and dioestrus day 2, without concomitant changes in GFR. As the plasma vasopressin concentrations produced by hormone infusion were similar on each day of the cycle, the renal responsiveness to vasopressin appears to vary over the 4 days of the oestrous cycle. This may be important in terms of alteration and possible disturbances of fluid balance which may occur during reproductive cycles and pregnancy.

Animals↗
PubMed1996

Effect of dietary restriction on benzo[a]pyrene (BaP) metabolic activation and pulmonary BaP-DNA adduct formation in mouse.

Hepatic microsomal xenobiotic metabolizing enzyme activities of laboratory animals can be modulated by Dietary restriction (DR). The modulation of xenobiotic metabolizing enzyme activities can affect the metabolic activation of chemical carcinogens. Acute DR (60% of the food consumption of ad libitum (AL)-fed mice for 7 weeks) reduced the body weights of the male B6C3F1 mice, and increased mouse pulmonary cytochrome P4501A1-dependent BaP metabolizing enzyme activity. The effects of DR on the formation of the specific BaP-DNA adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (BaP-N2-dG) in mouse lung can be detected by using 32P-postlabeling technique. In both AL- and DR-mice total BaP-DNA adduct formation in lung reached a peak at 48 hours after treatment with [3H]BaP and the in vivo formation of BaP-N2-dG was greater in DR mouse lung than in that of AL-animals by 22%. DR increased in vitro BaP-N2-dG formation by 39% when calf-thymus DNA was incubated with BaP using liver microsomes obtained from DR- or AL-mice as the enzyme source. The formation of the specific BaP-N2-dG adducts, measured by 32P-postlabeling, was only 20% of the total [3H]BaP-DNA adducts as determined by liquid scintillation counting. The increase of BaP-DNA adduct formation in mouse lung was correlated to the enhancement of the mouse pulmonary BaP metabolizing enzyme activity. Our results indicated that the effect of DR on the metabolic activation of BaP in mouse lung was dependent upon the mouse lung cytochrome P4501A1-dependent BaP metabolizing enzymes activities which was significantly increased by DR.

Animals↗
PubMed1996

Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms.

Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no-flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical-triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free-radical reactions, DNA cleavage, and transient extracerebral organ malfunction? For future mechanism-oriented studies of the brain after cardiac arrest and innovative cardiopulmonary-cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points.

Altitude Sickness↗
PubMed1996

[Enhancement of antitumor effect of cisplatin on human ovarian cancer by cyclosporin A in vitro and in vivo].

OBJECTIVES: To investigate the enhanced impact of cyclosporin A (CsA) on antitumor activity of cisplatin (DDP) for human ovarian cancer cells. METHODS IN VITRO STUDIES: human ovarian adenocarcinoma cells (COC1) and its resistant subline (COC1/DDP) were cultured separately with 4 different preparations: (1) normal saline; (2) CsA alone; (3) DDP alone; (4) DDP plus CsA. After 72 hours, the numbers of tumor cells were counted under microscope. Furthermore, 3H-thymidine incorporation tests were performed on the above 4 systems, and the inhibitory rate of tumor growth were calculated. In vivo studies: normal saline or 2mg/kg of DDP and 5mg/kg of CsA was injected intraperitoneally to nude mice with COC1/DDP xenograft cancer every 3 day for 3 times. The changes of tumor volumes and its pathological appearances were compared before and after treatment. RESULTS: IN VITRO STUDIES, DDP combined with CsA exhibited a synergistic cytotoxic effect on COC1 and COC1/DDP cells. The decrease of tumor cell numbers reached 24%-36%, 48%-60% of controls respectively. The inhibitory rates of DNA synthesis of these tumor cells, measured by 3H-TdR incorporation tests, were greater in DDP plus CsA group than those in DDP alone group (64.7% 63.9% versus 39.6% 25.1%, P < 0.01). The greater inhibitory rates of CsA+DDP regimen (81.4%) was also shown in vivo studies when compared with DDP alone regimen (49.1%) (P < 0.01). There were significant decreases of tumor cell density and nuclear mitosis in the combined group as compared with that of the DDP alone group (P < 0.01). CONCLUSIONS: The combination of DDP with 2 micrograms/ml of CsA yields enhancement of antitumor effect on human ovarian cancer. This study suggests that CsA may be used clinically as an antitumor enhancement of DDP for the treatment of ovarian adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Characteristics of the inward-rectifying potassium current in mouse ventricular myocytes and its relation to early after-depolarization.

The properties of the inward-rectifying potassium current (IK1) were studied in the single myocytes isolated from adult mouse ventricles by the whole-cell patch-clamp technique for the first time. Most of the properties of IK1 including channel conductances, activation, inactivation, rectification and external K+ sensitivity in mouse ventricular myocyte were similar to those in other species, but the current-voltage (I-V) curve of mouse ventricular myocyte showed no negative slope, i.e the slope in the range of membrane potential 50 mV positive to the reversal potential (VRev) was virtually flat and remained at a low current level ((59 +/- 39) pA). Under the superfusion of Tyrode's solution with 3 mmol/L K+ and 3 mmol/L Cs+, IK1 in the above region nearly decreased to zero, and then the early after-depolarization (EAD) occurred. The results suggest that this distinctive characteristic of IK1 in mouse ventricular myocyte may relate to the high susceptibility to EAD in mouse myocardium. The inhibition of IK1 seems to be a prerequisite for the occurrence of EAD in this experiment.

Action Potentials↗