Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 199 records · Page 11Linked to original sources

PubMed1998

The increase in angiotensin type-2 receptor mRNA level by glutamate stimulation in cultured rat cortical cells.

The changes in the angiotensin type-2 (AT2) receptor mRNA level during glutamate neurotoxicity in cultured rat cortical cells are examined to assess the possible involvement of AT2 receptor in cell injury. The day 10-14 cortical neurons were exposed to glutamate at a toxic concentration of 100 microM for 15 min. The viability of the culture was reduced by 60% after 24 h. AT2 receptor mRNA was then increased 2-fold after exposure to glutamate, while the maximum increase was observed in a dose-dependent manner (50-1000 microM) 3 h after glutamate stimulation. AT2 receptor binding also increased 3-12 h after glutamate exposure. The results suggest that the increase in the AT2 receptor preceded to some extent the insult of the cell after exposure. The increase in the mRNA level was suppressed by MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, thus indicating the possible involvement of NMDA receptor. The increase in the mRNA level was also antagonized by N-nitro L-arginine methyl-ester, a nitric oxide synthase inhibitor. The hemoglobin, a nitric oxide trap, inhibited the increase in the mRNA level. These results suggest that the increase in the mRNA level is associated with the nitric oxide synthesis by glutamate exposure. The viability of cortical cells after glutamate stimulation was partially restored by the AT2 receptor antagonist and by the antisense oligonucleotide for the AT2 receptor. The present results thus suggest that the AT2 receptor may in some way be related to one of the processes in cell injury caused by glutamate.

Angiotensin II↗

PubMed1998

Novel mechanism of HERG current suppression in LQT2: shift in voltage dependence of HERG inactivation.

In a Xenopus oocyte heterologous expression system, we characterized the electrophysiology of 3 novel missense mutations of HERG identified in Japanese LQT2 families: T474I (within the S2-S3 linker), A614V, and V630L (in the outer mouth of pore-forming region). For each of the 3 mutations, injection of mutant cRNA alone did not express detectable currents. Coinjection of wild-type (WT) along with each mutant cRNA (T474I/WT, A614V/WT, and V630L/WT) suppressed HERG current in a dominant-negative manner, and the order of magnitude of current suppression was V630L/WT>A614V/WT>T474I/WT. In addition to decreases in slope conductance for all 3 mutants, the voltage dependence of steady-state inactivation was shifted to negative potentials for V630L/WT and A614V/WT. Consequently, channel availability at positive potentials was diminished, and inward rectification was enhanced for these 2 mutants. Thus, missense mutations of HERG caused dominant-negative suppression through multiple mechanisms. The shift in voltage dependence of HERG inactivation and the resulting enhanced inward rectification in A614V/WT and V630L/WT provide a novel mechanism for suppression of the HERG current carrying outward current during the repolarization phase of the action potential.

Animals↗

PubMed1998

Increased sensitivity to vincristine of MDR cells by the leukotriene D4 receptor antagonist, ONO-1078.

The leukotriene D4 (LTD4) receptor antagonist, 4-oxo-8-[p-(4-phenylbutyloxy)benzoylamino]-2-(tetrazol-5-yl) -4H-1-benzopyran hemihydrate (ONO-1078) is used for the treatment of allergic asthma and other immediate hypersensitivity diseases. We examined the effect of ONO-1078 on the sensitivity to vincristine (VCR) of MRP overexpressing multidrug-resistant CV60 and its parental drug-sensitive KB-3-1 cell lines. The sensitivity to VCR of KB-3-1 and CV60 cells was increased 13- and 15-fold, respectively, by ONO-1078 at the maximum non-toxic concentration (100 microM). The VCR sensitivity of multidrug-resistant KB-C2 cells that overexpressed P-gp was increased 2.6-fold by ONO-1078. The accumulation of VCR in KB-3-1, CV60 and KB-C2 cells was significantly increased by ONO-1078. The efflux of VCR from KB-3-1 cells was not inhibited, but that from CV60 cells was enhanced compared with that from KB-3-1 cells and was partially inhibited by ONO-1078. ONO-1078 competitively inhibited the ATP-dependent [3H]LTC4 uptake in membrane vesicles isolated from CV60 cells. These findings suggest that ONO-1078 inhibits the transporting activity of MRP and that ONO-1078 increases the sensitivity to VCR of KB-3-1 cells by increasing the VCR uptake in the cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Differential interactions of the C terminus and the cytoplasmic I-II loop of neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. I. Molecular determination.

Interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels were investigated using the Xenopus oocyte expression system. Gi3alpha was found to inhibit both N- and P/Q-type channels by receptor agonists, whereas Gbeta1 gamma2 was responsible for prepulse facilitation of N-type channels. L-type channels (alpha1C) were not regulated by Galpha or Gbeta gamma. For N-type, prepulse facilitation mediated via Gbeta gamma was impaired when the cytoplasmic I-II loop (loop 1) was deleted or replaced with the alpha1C loop 1. Galpha-mediated inhibitions were also impaired by substitution of the alpha1C loop 1, but only when the C terminus was deleted. For P/Q-type, by contrast, deletion of the C terminus alone diminished Galpha-mediated inhibition. Moreover, a chimera of L-type with the alpha1B loop 1 gained Gbeta gamma-dependent facilitation, whereas an L-type chimera with the N- or P/Q-type C terminus gained Galpha-mediated inhibition. These findings provide evidence that loop 1 of N-type channels is a regulatory site for Gbeta gamma and the C termini of P/Q- and N-types for Galpha.

Animals↗

PubMed1998

Differential interactions of the C terminus and the cytoplasmic I-II loop of neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. II. Evidence for direct binding.

The present study was designed to obtain evidence for direct interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels, using synthetic peptides and fusion proteins derived from loop 1 (cytoplasmic loop between repeat I and II) and the C terminus of these channels. For N-type, prepulse facilitation as mediated by Gbeta gamma was impaired when a synthetic loop 1 peptide was applied intracellularly. Receptor agonist-induced inhibition of N-type as mediated by Galpha was also impaired by the loop 1 peptide but only when applied in combination with a C-terminal peptide. For P/Q-type channels, by contrast, the Galpha-mediated inhibition was diminished by application of a C-terminal peptide alone. Moreover, in vitro binding analysis for N- and P/Q-type channels revealed direct interaction of Galpha with C-terminal fusion proteins as well as direct interaction of Gbeta gamma with loop 1 fusion proteins. These findings define loop 1 of N- and P/Q-type Ca2+ channels as an interaction site for Gbeta gamma and the C termini for Galpha.

Amino Acid Sequence↗

PubMed1998

Reversal of MRP-mediated vincristine resistance in KB cells by buthionine sulfoximine in combination with PAK-104P.

The mechanism of multidrug resistance protein (MRP)-mediated multidrug resistance (MDR) is still unclear. MRP reportedly transports some GSH conjugates. Recently, we demonstrated that a pyridine analog, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl 5-(trans-4,6-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4 -(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P), that reversed P-glycoprotein (P-gp)-mediated MDR directly interacted with MRP and completely reversed the vincristine (VCR) resistance in MRP-mediated MDR C-A120 cells. We investigated the reversing effect of PAK-104P in C-A120 cells in combination with buthionine sulfoximine (BSO), another MDR-reversing agent with a different reversing mechanism. In immunoblots, MRP was overexpressed in C-A120 cells. The level of ATP-dependent [3H]VCR uptake was high in membrane vesicles from KB-C2 cells, but low in those from C-A120 and parental KB-3-1 cells. The sensitivity to VCR of C-A120 cells, but not of KB-C2 cells, was considerably increased by 100 microM BSO. VCR accumulation in C-A120 cells, but not in KB-C2 cells, was also enhanced by BSO. BSO did not inhibit ATP-dependent [3H]LTC4 uptake in C-A120 vesicles. The combination of BSO with PAK-104P at their low concentrations resulted in complete reversal of VCR resistance in C-A120 cells. These findings suggested that BSO might not directly interact with MRP and reversed resistance in MRP-mediated MDR cells by reducing the intracellular glutathione (GSH) level that was needed for the transport of drugs by MRP and suggested a role for the combination of drug resistance-modulating agents with different reversing mechanisms in the reversal of MRP-mediated MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Emergence of immunoreactivities for phosphorylated tau and amyloid-beta protein in chronic stage of fluid percussion injury in rat brain.

Head injury is one of the potential environmental factors in Alzheimer's disease (AD). To study the chronic stage of concussive brain injury, histological analyses were performed 2-6 months after right lateral fluid percussion (FP) brain injury (3.6-4.8 atm) in rats. Six months after injury, numerous normal-looking neurons in the telencephalon and brain stem were immunoreactive with either antibody to phosphorylated tau or with four antibodies to beta-amyloid protein. Neuronal counts in the cortices were gradually decreased after injury, up to 42% loss at 6 months after injury. These neuropathological changes suggest that this animal model could serve as a good animal model of neurodegenerative diseases such as AD.

Amyloid beta-Peptides↗

PubMed1998

Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer.

Using the method of microsatellite analysis, we studied 40 tissues with pancreatic ductal adenocarcinoma and identified two commonly deleted regions on the long arm of chromosome 12. One (region A) was found between D12S81 and D12S1719 at 12q21 at a frequency of 67.5%, and the other (region B) was located between D12S360 and D12S78 at 12q22-q23.1 at a frequency of 60%; the latter was reported previously (M. Kimura, et al. Genes Chromosomes Cancer, 17: 88-93, 1996). The results of microsatellite analyses were verified by fluorescence in situ hybridization. We further analyzed 19 pancreatic cancer cell lines by fluorescence in situ hybridization and found that 10 of them showed allelic loss at D12S81 and 6 showed allelic loss at D12S360. Yeast artificial chromosome contigs were constructed to cover the deleted regions. Region B was completely covered by a 650-kb yeast artificial chromosome clone. The frequently deleted regions in chromosome 12q in pancreatic cancer that were identified here may provide new avenues for isolating novel tumor suppressor genes.

Adult↗

PubMed1998

Premorbid personality traits of patients with organic (ICD-10 F0), schizophrenic (F2), mood (F3), and neurotic (F4) disorders according to the five-factor model of personality.

The present article aims to examine premorbid personality traits of psychiatric patients with various diagnoses by asking their close relatives to retrospectively rate the patients' usual self with a questionnaire designed for the five-factor model of personality, a rapidly emerging comprehensive theory of personality structure. Data for 140 patients and 84 controls were analyzed. Although psychiatric patients as a group were characterized by high neuroticism and low conscientiousness when compared with the healthy controls, there were only a few traits that distinguished a particular diagnostic group from either the normal control or from the rest of the patients: neurotic disorder patients had higher neuroticism scores than the normal controls; unipolar depressives had a higher conscientiousness score than the rest of the patient group. No salient premorbid trait was noted for patients with organic mental disorders, schizophrenic disorders or bipolar disorders.

Adult↗

PubMed1998

An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells.

The mechanism for cisplatin resistance in cisplatin-resistant KCP-4 cells was studied. Although multidrug resistance-associated protein (MRP) was not detected in KCP-4 cells, the cells were more resistant to heavy metals than multidrug-resistant C-A120 cells that overexpressed MRP. KCP-4 cells expressed metallothionein, but it was scarcely involved in cisplatin resistance in these cells. KCP-4 cells did not express canalicular multispecific organic anion transporter (cMOAT). The glutathione (GSH) level was 4.7-fold higher in KCP-4 cells than in KB-3-1 cells. When the GSH level in KCP-4 cells was decreased by treating the cells with buthionine sulfoximine and nitrofurantoin, the accumulation of and sensitivity to cisplatin in the cells were increased. C-A120 cells were only 3.0-fold more resistant to cisplatin than KB-3-1 cells and this resistance was not affected by the increased glutathione level. The accumulation of platinum in C-A120 and KCP-4 cells was 68.5 and 20.4% of that in KB-3-1 cells, respectively, while the intracellular levels of antimony potassium tartrate in C-A120 and KCP-4 cells were 13.2 and 9.9% of that in KB-3-1 cells, respectively. The ATP-dependent efflux of antimony was enhanced in both C-A120 and KCP-4 cells. These results, taken together, suggest an efflux pump for heavy metals different from MRP and cMOAT is involved in cisplatin resistance in KCP-4 cells.

ATP-Binding Cassette Transporters↗

PubMed1998

The expression of multidrug resistance protein in human gastrointestinal tract carcinomas.

BACKGROUND: Multidrug resistance protein (MRP) is a membrane phosphoglycoprotein with an Mr of 190,000 that is involved in the non-P-glycoprotein mediated multidrug resistance of human tumor cells. The aim of this study was to determine the clinicopathologic relevance of MRP expression in human gastrointestinal tract carcinomas. METHODS: The authors prepared a rabbit antiserum against MRP that does not cross-react with P-glycoprotein and retrospectively examined the expression of MRP in 86 squamous cell carcinomas of the esophagus, 103 adenocarcinomas of the stomach, and 139 colorectal adenocarcinomas by immunohistochemistry. None of the patients in this study had received prior chemotherapy. RESULTS: The proportion of MRP positive samples in the squamous cell carcinomas of the esophagus (62.8%, 54 of 86) was significantly higher than that in the adenocarcinomas of the stomach (34.1%, 35 of 103) and the colorectal adenocarcinomas (40.3%, 56 of 139) (P <0.01). The proportion of MRP positivity in the well-differentiated carcinomas was significantly higher than that in moderately or poorly differentiated carcinomas. MRP expression was independent of gender, lymph node metastasis, and tumor progression. CONCLUSIONS: These data indicate that the expression of MRP is correlated with the differentiation of carcinoma cells in the gastrointestinal tract and may be involved in the intrinsic drug resistance of well-differentiated squamous cell carcinoma of the esophagus.

ATP-Binding Cassette Transporters↗

PubMed1998

Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin-producing tumors of the pancreas.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative pancreatoscopy with the ultrathin pancreatoscope for the main pancreatic lesions of mucin-producing tumors of the pancreas (MPT). DESIGN: Prospective diagnostic test study with a criterion standard of pathologic examination and masked comparison. SETTING: A university hospital. PATIENTS: Twenty-four consecutive patients with MPT referred for surgery in whom endoscopic retrograde pancreatography, endoscopic ultrasonography, and computed tomography had been performed as a diagnostic examination. All patients underwent surgery and the diagnosis was confirmed by pathologic examination. INTERVENTION: Intraoperative pancreatoscopy was performed with the ultrathin pancreatoscope. MAIN OUTCOME MEASURES: Findings of intraoperative pancreatoscopy, endoscopic retrograde pancreatography, and endoscopic ultrasonography were confirmed by pathologic examination of resected specimens. The diagnostic accuracy of these 3 modalities in detection of MPT lesions in the main pancreatic duct was compared. RESULTS: The diagnostic criterion of MPT lesions in the main pancreatic duct by intraoperative pancreatoscopy was a granular and papillary mural nodule. An MPT lesion in the main pancreatic duct was found in 17 of 24 cases. Intraoperative pancreatoscopy detected 10 cases of intraductal MPT lesions that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. Five of 10 cases were intraductal multicentric lesions. In 3 of these 5, additional pancreatic resection was performed. For diagnosis of MPT lesions, the sensitivity, specificity, and overall accuracy of intraoperative pancreatoscopy were all 100%; respective values were 43.8%, 100%, and 60.9% for endoscopic retrograde pancreatography and 47%, 100%, and 62.5% for endoscopic ultrasonography. CONCLUSIONS: Intraoperative pancreatoscopy is safe and effective in diagnosing the intrapancreatic duct extension and multicentric lesions of MPT. It provides important information for operative strategy and contributes to successful pancreatic surgery.

Adult↗

PubMed1998

Antitumor spectra of anthracyclines against gastric cancer tissues obtained from surgical specimens with reference to P-glycoprotein expression.

BACKGROUND AND OBJECTIVES: Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression. METHODS: Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP. RESULTS: A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR. CONCLUSIONS: The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

Bioactive bone cement: comparison of apatite and wollastonite containing glass-ceramic, hydroxyapatite, and beta-tricalcium phosphate fillers on bone-bonding strength.

A study was conducted to compare the bone-bonding strengths of three types of bioactive bone cement, consisting of either apatite- and wollastonite-containing glass-ceramic (AW-GC) powder, hydroxyapatite (HA) powder, or beta-tricalcium phosphate (beta-TCP) powder as an inorganic filler and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. Seventy percent (w/w) filler was added to the cement. Rectangular plates (10 x 15 x 2 mm) of each cement were made and abraded with #2000 alumina powder. After soaking in simulated body fluid for 2 days, the AW cement (AWC) and HA cement (HAC) formed bonelike apatite over their entire surfaces, but the TCP cement (TCPC) did not. Plates of each type of cement were implanted into the tibial metaphyses of male Japanese white rabbits, and the failure loads were measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, HAC, and TCPC were 3.95, 2.04, and 2.03 kgf at 10 weeks and 4.36, 3.45, and 3.10 kgf at 25 weeks, respectively. The failure loads of the AWC were significantly higher than those of the HAC and TCPC at 10 and 25 weeks. Histological examination by contact microradiogram and Giemsa surface staining of the bone-cement interface revealed that all the bioactive bone cements were in direct contact with bone. However, scanning electron microscopy and energy-dispersive X-ray microanalysis showed that only AWC had contacted to the bone via a Ca-P rich layer formed at the interface between the AW-GC powder and the bone, which might explain its high bone-bonding strength. Neither the HAC nor the TCPC contacted the bone through such a layer between each powder and the bone, although the HAC and TCPC directly contacted with bone. Our results indicate that all three types of abraded and prefabricated cement have bonding strength to bone, but AWC has superior bone-bonding strength compared to HAC and TCPC.

Animals↗

PubMed1998

Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer.

In human endometrial cancer, we have previously identified a 790-kb region of common allelic loss in chromosome bands 10q25-q26, flanked by D10S587 and D10S1723. We constructed a contig covering the entire deleted region using YACs, PACs, and BACs. Five overlapping cosmid clones derived from YAC clones completely covered the entire deleted region: its size was estimated to be no larger than 200 kb. We further performed two-color fluorescence in situ hybridization (FISH) analysis to confirm the deletion and narrowed down the deleted region to 100 kb or less; it was covered by three overlapping cosmid clones that were included in one BAC clone. Restriction endonuclease mapping identified a region in which NotI, SalI, SmaI, and Xhol were clustered, suggesting the possible existence of a CpG island.

Chromosome Banding↗

PubMed1998

Typus melancholicus in light of the five-factor model of personality.

The present paper examines Typus melancholicus (TM), which is widely accepted as premorbid personality of depression in Germany and Japan, from the view-point of the five-factor model of personality, which has recently been gaining international popularity as the comprehensive model of personality traits. Two measures of TM, von Zerssen's F-list and Kasahara's scale, as well as the personality questionnaire for the five-factor model, NEO Five Factor Inventory, were completed for 140 consecutive psychiatric outpatients by their close relatives. It was found that (a) the two measures of TM had good internal consistency reliability, (b) they had reasonable concurrent validity, and (c) TM was characterized by high Conscientiousness, high Agreeableness and, to a lesser degree, high Extraversion. The results were largely in agreement with theoretical prediction and provide further support to the construct validity of the TM measures. Whether combining the three personality traits into one type is meaningful in depicting a particular premorbid personality constellation awaits further empirical examination.

Adult↗

PubMed1998

Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma.

We have investigated the mRNA/protein expression of several tyrosine kinase receptors, growth factors, and p16INK4A cyclin inhibitor in cell lines derived from normal human pancreatic duct epithelium (HPDE) and compared them with those of five pancreatic ductal carcinoma cell lines. Cultured HPDE cells express low levels of epidermal growth factor receptor (EGFR), erbB2, transforming growth factor (TGF)-alpha, Met/hepatocyte growth factor receptor (HGFR), vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF). They also expressed high levels of amphiregulin but did not express EGF and cripto. The expression levels were similar in primary normal HPDE cells and those expressing transfected E6E7 genes of human papilloma virus-16, but their immortalization appeared to enhance the expression of EGFR and Met/HGFR. In comparison, pancreatic carcinoma cell lines commonly demonstrated overexpression of EGFR, erbB2, TGF-alpha, Met/HGFR, VEGF, and KGF, but they consistently showed marked down-regulation of amphiregulin mRNA expression. In contrast to all carcinoma cell lines that showed deletions of the p16 gene, HPDE cells consistently demonstrated normal p16 genotype and its mRNA expression. This is the first report that compares the phenotypic expression of cultured pancreatic ductal carcinoma cells with epithelial cell lines derived from normal human pancreatic ducts. The findings confirm that malignant transformation of human pancreatic duct cells commonly results in a deregulation of expression of various growth factors and receptors.

Adenocarcinoma↗

PubMed1998

Role of cardiac chloride currents in changes in action potential characteristics and arrhythmias.

Various types of Cl- currents have been recorded in cardiac myocytes from different regions of the heart and in different species. With few exceptions, most of these currents are not active under basal conditions, but are activated under the influence of various agonists and by physical stress. These channels are distributed nonuniformly, depending on the cell type, tissue and region of the heart. Therefore, Cl- current activation may influence membrane potential and impulse formation differently in different cells, and may play a role in arrhythmogenesis. Among these Cl- currents, the protein kinase A-activated Cl- current (I Cl.PKA), the stretch- or swelling-activated Cl- current (I Cl.SWELL) and the Ca(2+)-activated Cl current (I Cl.Ca) comprise the major anion currents that modify cardiac electrical activity. These currents exhibit outward-going rectification, or are predominantly activated at depolarized voltages and, thus, contribute significantly to shortening of the action potential duration but little to diastolic depolarization. The action potential shortening by Cl- current activation may not only perpetuate reentry by shortening the refractory period in a reentry pathway, but may also prevent the development of early afterdepolarization and triggered activity caused by the prolongation of action potentials. I Cl.Ca contributes to delayed afterdepolarization at diastolic potentials in Ca(2+)-overloaded cells. Another factor limiting the influence of Cl- currents on diastolic potentials is the presence of a predominantly opposing background K+ current, except at the nodal regions that lack these K+ channels, or under conditions of decreased K+ conductance. Therefore, the contribution of Cl- currents to the genesis of arrhythmias may depend on their association with the conductance of other ions, especially that of K+.

Action Potentials↗