Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on membrane currents and on single channel K currents in smooth muscle cells isolated from canine trachea were examined by use of tight seal whole cell- and patch-clamp techniques. 2. Depolarizing current applied through a recording pipette did not elicit an action potential under current clamp. A strong outward rectification was observed. 3. In most cells under voltage-clamp, only an outward current was observed upon depolarization from -60 mV when a pipette solution contained mainly KCl. The outward current consisted of three components; a large initial transient, a following sustained component and an additional component of irregular small transients on the sustained one. The two transient components were almost abolished when extracellular and pipette solutions contained 2.2 mM Cd2+ (0 mM Ca2+) and 10 mM EGTA, respectively. The sustained component was well maintained under these conditions. 4. TEA at low concentrations (less than 1 mM) effectively decreased the transient components and made the outward current smooth; it also suppressed the sustained component at higher concentrations. In outside-out patches, external 1 mM TEA reduced the single channel conductance of Ca-activated K channels by about 87% whereas 3 mM 4-AP did not. 4-AP at low concentrations (less than 3 mM) selectively reduced the sustained component of the outward current. 5. A Ca current recorded after the suppression of outward current by internal Cs+ had a peak of approximately 200 pA at +10 mV (holding potential: -60 mV). The half inactivation voltage in the steady-state was approximately -30 mV. 6. Simultaneous application of 1 mM TEA and 4-AP reduced the outward current and unmasked a Ca current. Under these conditions, an action potential with overshoot was easily elicited under current clamp. 7. It is concluded that the low excitability of canine tracheal smooth muscle cell upon depolarization is due to a large outward K current which consists of Ca-dependent and Ca-independent components. The peak amplitude of the Ca current is similar to that in highly excitable smooth muscle cells such as those of the ureter.
 ...
PMID:Effects of tetraethylammonium and 4-aminopyridine on outward currents and excitability in canine tracheal smooth muscle cells. 169 97

1. Calcium channel currents were recorded in single, enzymatically isolated smooth muscle cells of the guinea-pig ureter using a single-electrode whole-cell voltage clamp technique. Calcium and barium currents through voltage-activated Ca2+ channels were recorded in cells dialysed with Cs(+)- or Na(+)-containing saline which suppressed K+ currents. 2. Inward currents in Ca2+ (1.5-7.5 mM) or Ba2+ (1.5-7.5 mM) were recorded at potentials positive to -50 to -30 mV. Inward currents were maximal at 0 mV in 1.5 mM-Ca2+ and at +10 mV in 7.5 mM-Ba2+. Current flow through Ca2+ channels in Cs(+)-filled cells (in 1.5 mM-Ca2+ or 7.5 mM-Ba2+) changed from inward to outward at potentials positive to +70 mV. In Na(+)-filled cells this reversal potential was between +50 and +60 mV. 3. Replacing Ca2+ or Ba2+ with Co2+ (1.5 mM) blocked all inward current flow through these Ca2+ channels; outward currents at potentials positive to +40 mV, however, were increased. Cadmium (100 microM) and nifedipine (0.1-10 microM) reduced both inward and outward current flow. 4. Calcium channel activation showed a sigmoidal relationship with membrane potential; the potential of half-maximal activation was -8.4 mV in 1.5 mM-Ca2+ and -10.8 mV in 7.5 mM-Ba2+. The maximum membrane conductance to Ca2+ (in 1.5 mM-Ca2+) was 2.57 nS/cell or approximately 0.05 mS/cm2. 5. Evidence for a voltage-dependent inactivation mechanism included (a) the time-dependent relaxation of the outward currents at potentials positive to the reversal potential and (b) a steady-state inactivation (f infinity (V] vs. membrane potential relationship (in 7.5 mM-Ba2+) which ranged between -80 and 0 mV, with a half-maximal availability at -40.5 mV. 6. The voltage dependencies of the inward current elicited from -80 and -30 mV were similar, suggesting that depolarization activated only L-type Ca2+ channels. 7. It was concluded that the processes controlling the time course of the Ca2+ current in single ureteral cells bathed in physiological concentrations of Ca2+ were mostly voltage-dependent.
 ...
PMID:The whole-cell Ca2+ channel current in single smooth muscle cells of the guinea-pig ureter. 216 65

1. Two kinds of transient outward currents were observed upon depolarization of single smooth muscle cells isolated from guinea-pig ureter. The major transient outward current was through Ca2(+)-activated K+ channels (IK(Ca) which had a large conductance (130 pS; 126 mM [K+]i/5.9 mM [K+]o). 2. The smaller transient outward current (ITO) was pharmacologically separated from other membrane currents in the presence of 1 mM-Cd2+ and 2 mM-tetraethylammonium(TEA+) and was selectively blocked by 3 mM-4-aminopyridine. It peaked (approximately 200 pA) within 10 ms upon depolarization from -80 to +20 mV and its half-inactivation time was approximately 50 ms at +20 mV. Half-maximum voltages (V 1/2) for activation and inactivation were about -8 and -50 mV, respectively, in the presence of 1 mM-Cd2+ and 2 mM-TEA+. The time course of recovery from inactivation of ITO was fitted with a single-exponential function (tau = 100 ms at -80 mV). A tenfold change of [K+]o resulted in a 53 mV change in the reversal potential of the tail of ITO. 3. Cadmium reduced peak ITO and shifted the voltage dependence of activation and inactivation in the positive direction in a concentration-dependent manner. The V 1/2 for inactivation in the absence of Cd2+ was estimated to be approximately -64 mV. 4. Single-channel outward currents which appeared only in the initial part of a depolarizing pulse from about -100 mV were recorded using the cell-attached patch clamp. The decay of the ensemble average of the current was similar to the macroscopic ITO under whole-cell clamp. When the holding potential was less negative, the opening probability of the channel greatly decreased. The channel conductance in normal extracellular medium was 14 pS. 5. In ureter cells ITO resembles A-type current. ITO does not contribute significantly to the repolarization of the action potential but it may regulate membrane excitability by opposing Ca2+ current activated around the threshold of the action potential.
 ...
PMID:Characteristics of transient outward currents in single smooth muscle cells from the ureter of the guinea-pig. 221 1

An attempt was made to obtain electrophysiological evidence for continuous influx of Ca ion through voltage-dependent Ca channel (VDCC) in smooth muscle during long depolarization, for example in high K solution. Noninactivated Ca current [ICa(ni)] remaining after the accomplishment of voltage-dependent inactivation by prolonged depolarization for approximately 1 min was detected by three means under whole cell voltage clamp in several types of smooth muscle cells. The measurement of ICa(ni) was performed by micropuff application of Cd2+ or Ca2+ in the presence or absence of 5 mM extracellular Ca, respectively, or jump of extracellular Ca concentration [( Ca]o). The current-voltage relationship of ICa(ni) evaluated by these means had a peak at approximately -10 mV. The peak amplitude ranged from 5 to 25 pA, depending on whether the cells were isolated from guinea pig urinary bladder, ureter, vas deferens, taenia caecum, or rabbit portal vein. The ICa(ni) may be large enough to explain sustained contraction in high K solution, at least in these smooth muscle tissues. A window current simulated from the steady-state activation and inactivation curves and the maximum conductance of Ca current (ICa) in these cells suggests a theoretical basis for the observed ICa(ni).
 ...
PMID:Measurement and simulation of noninactivating Ca current in smooth muscle cells. 246 90

1. Ionic currents underlying the action potential were recorded from enzymatically isolated smooth muscle cells of guinea-pig ureter. 2. The action potential recorded from a single cell was similar to that from a multicellular preparation. It showed repetitive spikes on a plateau potential which followed the first spike. Treatment with 10 mM-tetraethylammonium (TEA) increased the amplitude and duration of the plateau phase and abolished the repetitive spikes. 3. Under voltage clamp mode, at least two (maybe three) kinds of outward currents were activated during depolarizing pulses. The main outward current was Ca2+-dependent K+ current (IK(Ca], which was mostly blocked in Ca2+-free solution, or by application of 1 mM-cadmium (Cd2+) or 2 mM-tetraethylammonium (TEA). IK(Ca) was greatly decreased by treatment with 5 mM-caffeine or an addition of 10 mM-EGTA in a pipette solution. 4. In the presence of 1 mM-Cd2+ and 2 mM-TEA, a small transient outward current remained. 4-Aminopyridine (1 mM) suppressed the transient outward current by about 40%. Time- and voltage-dependent delayed rectifier outward currents were small in ureter cells. An inwardly rectifying K+ current was not detected. 5. An application of 1 mM-Cd2+, 5 mM-cobalt (Co2+), 1 mM-lanthanum (La3+) or 0.1 microM-nifedipine completely blocked the action potential. Replacement of 80-90% of extracellular Na+ with Li+ or Tris almost abolished the plateau potential and repetitive spikes but did not change significantly the first spike. 6. In the presence of 30 mM-TEA, the inward current elicited by depolarization was monophasic and lasted for more than 1 s. Application of 1 mM-Cd2+, 1 mM-La3+, 0.1 microM-nifedipine, or 5 mM-Co2+ completely blocked inward current. The replacement (87%) of extracellular Na+ ions with Li+, Tris, sucrose or TEA speeded up the decay of inward current; the inward current decreased by 10-60% at the end of a 500 ms pulse. 7. Even in low-Na+ solution (120 mM-TEA), the inactivation of ICa had a quite slow component (tau = 1 s), in addition to another faster component (tau = 100 ms) at 0 mV. When short depolarizing clamp pulses (50 ms) were repetitively applied at short intervals (50 ms) and with interpulse voltage of -10 or -20 mV to mimic the repetitive spikes on the plateau of the action potential, the decline of peak Ca2+ current during the train of pulses was smaller than the decay of Ca2+ current during a long pulse.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Ionic currents in single smooth muscle cells from the ureter of the guinea-pig. 248 52

To clarify the mechanism of mobilization of renal and hepatic cadmium (Cd) by N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) in mice exposed to Cd, the effects of pretreatment with probenecid, an organic anion transport inhibitor, or with acivicin, a gamma-glutamyltranspeptidase (gamma-GTP) inhibitor and ureter-ligation were investigated on the excretion and distribution of chelating agents and Cd. The renal contents of BGD and HBGD were increased by ureter-ligation and decreased by acivicin pretreatment. The mobilizing effect of BGD on the renal Cd was inhibited by probenecid pretreatment. The action of HBGD in removing Cd from the kidney was inhibited by both probenecid pretreatment and ureter-ligation. These results suggest that BGD and HBGD are mainly taken up into the renal tubular cells through the basolateral membrane which is dependent on the action of gamma-GTP; that the Cd-BGD complex formed in the tubular cells is secreted by a probenecid-sensitive organic anion transport system through the basolateral membrane; and that the Cd-HBGD complex formed in the tubular cells is secreted to the tubular lumen by an organic anion transport system through the brush border membrane. Probenecid pretreatment increased the hepatic contents of BGD and HBGD and also promoted the effects of these chelating agents in removing Cd from the liver, indicating an inhibitory effect of probenecid on the glucuronidation of BGD and the secretion of HBGD from the kidney. These results suggest that BGD and HBGD are taken up into the liver and secreted from the organ to the bile by a transport system other than a probenecid-sensitive transport mechanism.
 ...
PMID:Mechanism of mobilization of renal and hepatic cadmium by dithiocarbamates in mice. 790 46

1. We have investigated the origin of the intracellular acid pH transients that accompany myometrial contraction. Intra- and extracellular pH were measured with SNARF and intracellular Ca2+ concentration ([Ca2+]i) with indo-1. 2. An intracellular acidification accompanied spontaneous contractions and those elicited by KCl depolarization or the addition of the agonists carbachol or prostaglandin F2 alpha. The size of the acidification increased with the magnitude of the contraction. 3. The intracellular acidification was accompanied by an extracellular alkalinization, showing that it results from proton movement across the surface membrane. Furthermore, it was decreased either by addition of Cd2+ (20 nM, an inhibitor of the sarcolemmal Ca(2+)-ATPase) or by elevating [Ca2+]o. 4. Extracellular alkalinization increased the magnitude of the rise of [Ca2+]i and force produced by KCl. 5. An intracellular acidification was also associated with contraction in the portal vein and ureter. 6. We conclude that the sarcolemmal Ca(2+)-ATPase produces a significant intracellular acidification while removing Ca2+. Both the acidification and decrease of [Ca2+]i will promote relaxation. Since Ca2+ and protons have opposite effects on many cellular processes, this dual regulation by these two ions may be of general importance.
 ...
PMID:The role of the sarcolemmal Ca(2+)-ATPase in the pH transients associated with contraction in rat smooth muscle. 942 76

In three separate sets of studies, the effects of ureteral ligation and coadministration of cadmium with cysteine or glutathione (GSH) (in either a 4:1 or 2:1 ratio of thiol to cadmium) on the renal disposition of cadmium were assessed in rats 1 h after the administration of cadmium. In all experiments, co-administration of cadmium with either cysteine or GSH caused the renal accumulation of cadmium to increase significantly (by approximately 60-70%) 1 h after injection. Moreover, in all experiments in which both ureters had been ligated in a rat prior to the administration of cadmium, the net total renal accumulation of cadmium was only about 20% less than that in control animals that had not undergone bilateral ureteral ligation when cadmium was administered as cadmium chloride. Furthermore, in animals in which only one ureter had been ligated, the net accumulation of cadmium in the kidney whose ureter had been ligated was between 25 and 30% less than that in the contralateral kidney. Coadministration of cadmium with cysteine or GSH also caused the net accumulation of cadmium to be increased in rats whose ureter(s) had been ligated. Overall, the present findings indicate that there is a significant basolateral component in the acute, in vivo, renal tubular uptake of cadmium. Moreover, the findings indicate that the basolateral uptake of cadmium is enhanced when cadmium is coadministered with cysteine or GSH.
 ...
PMID:Evidence for basolateral uptake of cadmium in the kidneys of rats. 1073 40

The structural characteristics of several dithiocarbamates (DTCs) [N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD)] that induce in vivo mobilization of cadmium (Cd) were examined in mice. The renal and hepatic contents of Cd were lower in the treatments with Cd-DTC combinations than in that with Cd alone. Probenecid pretreatment decreased the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, but it increased the renal content of Cd and decreased the urinary excretion of the metal in Cd-HBGD and Cd-CBGD treated mice. Furthermore, although ureter-ligation did not affect the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, it increased the renal content of Cd in Cd-HBGD and Cd-CBGD treated mice. These findings suggest that Cd-MBGD and Cd-BGD complexes are taken up into the tubular cells by an organic anion transport system through the basolateral membrane, whereas Cd-HBGD and Cd-CBGD complexes are secreted to the tubular lumen by an organic anion transport system through the brush border membrane. The results of probenecid pretreatment also led us to assume that the hepatic transport of these four Cd-DTC complexes is regulated, at least in part, by a probenecid-sensitive organic anion transport system.
 ...
PMID:Structure-effect relationship in the mobilization of cadmium in mice by several dithiocarbamates. 1203 85