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81.
Mark Jorissen Johan Vereecke Edward Carmeliet Herman Van den Berghe Jean -Jacques Cassiman 《Pflügers Archiv : European journal of physiology》1990,415(5):617-623
The apical membranes of cultured human nasal epithelial cells from adults and fetuses were investigated with the patch-clamp
technique. Amiloride-insensitive, calcium- and voltage-dependent, non-selective cation channels were found in 4% of the cell-attached,
and 18% of the inside-out and outside-out patches (n=412). Multiple functional channels were present in more than 90% of these patches, with a mean of 3.9 channels per patch
(n=55). The current-voltage relationship can be described by the Goldman equations and the single channel conductance was 20.1±0.3
pS (n=29) in adult and 20.7±0.4 pS (n=44) in fetal cells in symmetrical 150mM NaCl solutions. The channels were highly selective for cations: PNa/PCl was 30 in adult and 45 in fetal experiments. They were equally permeable for K+ and Na+, somewhat less for Cs+, and impermeable for choline+ and tetraethylammonium+. The open probability was voltage dependent: it increased approximately 2-fold with 30mV depolarization in the potential
range from −60mV to +60mV. The channels were activated by Ca2+ concentrations of about 10−4M at the cytoplasmic side, but were insensitive to extracellular Ca2+ and amiloride (10−4M). The non-selective cation channels found in apical membranes of cultured fetal nasal epithelial cells were not different
from the adult ones. 相似文献
82.
目的:探讨链脲佐菌素诱导的糖尿病早期小鼠胸主动脉钾通道的变化。方法:实验采用离体血管的方法测定糖尿病鼠和正常鼠胸主动脉环对血管收缩剂:60mmol/LKCl和苯肾上腺素(PE)、内皮非依赖性舒张剂:硝普钠(SNP)以及电压依赖性钾通道(KV通道),钙激活型钾通道(KCa通道),ATP敏感钾通道(KATP通道)阻断剂的反应。结果:糖尿病鼠胸主动脉环对60mmol/LKCl、PE和SNP的效应都显著大于对照组;KCa通道阻断剂四乙铵(TEA)显著降低糖尿病小鼠胸主动脉环在PE的激动下SNP的舒张效应,而且其-logIC50的差值较对照组显著增大;KV通道阻断剂4-氨基吡啶(4-AP)显著降低糖尿病和正常小鼠胸主动脉环对SNP的舒张效应,但是-logIC50差值无显著差异;KATP通道阻断剂格列苯脲(Glibenclamide)显著降低糖尿病小鼠胸主动脉环对SNP的舒张效应,而对照组无显著阻断作用,-logIC50的差值也无显著差异。结论:糖尿病早期小鼠胸主动脉平滑肌细胞KCa通道的开放或表达显著增强,也证实了KATP通道开放增强。 相似文献
83.
Two K+ channel populations were identified in depolarized cell-attached membrane patches of myocytes freshly dispersed from the circular smooth muscle of guinea-pig proximal colon. First, a large-conductance (150 pS) Ca2+-activated K+ channel which was non-inactivating and sensitive to blockade by tetraethylammonium (TEA, 0.5–5 mM); and second, a smaller conductance K+ channel which opened and closed within 100 ms, was insensitive to TEA (0.5–5 mM), but was blocked by 5 mM 4-aminopyridine (4-AP) or maintained depolarization, and which had a unitary conductance of 12–13 pS. The averaged time course of these smaller conductance K+ channels closely resembled the time course of the 4-AP-sensitive, Ca2+-insensitive transient outward K+ current recorded in the whole-cell recording mode. 相似文献
84.
Heinz Gögelein Bernd Pfannmüller 《Pflügers Archiv : European journal of physiology》1989,413(3):287-298
Nonselective Ca2+-sensitive cation channels in the basolateral membrane of isolated cells of the rat exocrine pancreas were investigated with the patch clamp technique. With 1.3 mmol/l Ca2+ on the cytosolic side, the mean openstate probabilityP
o of one channel was about 0.5. In insideout oriented cell-excised membrane patches the substances diphenylamine-2-carboxylic acid (DPC), 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 3,5-dichlorodiphenylamine-2-carboxylic acid (DCDPC) were applied to the cytosolic side. These compounds inhibited the nonselective cation channels by increasing the mean channel closed time (slow block). 100 mol/l of NPPB or DPC decreasedP
o from 0.5 (control conditions) to 0.2 and 0.04, respectively, whereas 100 mol/l of DCDPC blocked the channel completely. All effects were reversible. 1 mmol/l quinine also reducedP
o, but in contrast to the abov mentioned substances, it induced fast flickering. Ba2+ (70 mmol/l) and tetraethylammonium (TEA+; 20 mmol/l) had no effects. We investigated also the stilbene disulfonates 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid (SITS), 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS) and 4,4-dinitro-2,2-stilbenedisulfonate (DNDS). 10 mol/l SITS applied to the cytosolic side increasedP
o from 0.5 to 0.7 and with 100 mol/l SITS the channels remained nearly permanently in its open state (P
o1). A similar activation of the channels was also observed with DIDS and DNDS. These effects were poorly reversible. The stilbene disulfonates acted by increasing the channel mean open time. When the channel was inactivated by decreasing bath Ca2+ concentration to 0.1 mol/l, addition of 100 mol/l of SITS had no effect. Similarly, reducing bath Ca2+ concentration from 1.3 mmol/l in presence of 100 mol/l SITS (channels are maximally activated) to 0.1 mol/l, inactivated the channels completely. These results demonstrate, that SITS can only activate the channels in the presence of Ca2+. SITS had no effects, when applied to the extracellular side in outside out patches. In summary, the substances DPC, NPPB and DCDPC inhibit nonselective cation channels, where DCDPC has the most potent and NPPB the smallest effect; whereas SITS, DIDS and DNDS activate the channel when applied from the cytosolic side in the presence of Ca2+ ions. 相似文献
85.
Luis Gandía Baldomero Lara Julita S. Imperial Mercedes Villarroya Almudena Albillos Rosario Maroto A. G. García Baldomero M. Olivera 《Pflügers Archiv : European journal of physiology》1997,435(1):55-64
The characteristics of the binding sites for the Conus magus toxins ω-conotoxin MVIIC and ω-conotoxin MVIID, as well as their effects on K+-evoked 45Ca2+ entry and whole-cell Ba2+ currents (I
Ba), and K+-evoked catecholamine secretion have been studied in bovine adrenal chromaffin cells. Binding of [125I] ω-conotoxin GVIA to bovine adrenal medullary membranes was displaced by ω-conotoxins GVIA, MVIIC and MVIID with IC50 values of around 0.1, 4 and 100 nM, respectively. The reverse was true for the binding of [125I] ω-conotoxin MVIIC, which was displaced by ω-conotoxins MVIIC, MVIID and GVIA with IC50 values of around 30, 80 and 1.200 nM, respectively. The sites recognized by ω-conotoxins MVIIC and MVIID in bovine brain
exhibited higher affinities (IC50 values of around 1 nM). Both ω-conotoxin MVIIC and MVIID blocked I
Ba by 70–80%; the higher the [Ba2+]o of the extracellular solution the lower the blockade induced by ω-conotoxin MVIIC. This was not the case for ω-conotoxin
MVIID; high Ba2+ (10 mM) slowed down the development of blockade but the maximum blockade achieved was similar to that obtained in 2 mM Ba2+. A further difference between the two toxins concerns their reversibility; washout of ω-conotoxin MVIIC did not reverse the
blockade of I
Ba while in the case of ω-conotoxin MVIID a partial, quick recovery of current was produced. This component was irreversibly
blocked by ω-conotoxin GVIA, suggesting that it is associated with N-type Ca2+ channels. Blockade of K+-evoked 45Ca2+ entry produced results which paralleled those obtained by measuring I
Ba. Thus, 1 μM of each of ω-conotoxin GVIA and MVIIA inhibited Ca2+ uptake by 25%, while 1 μM of each of ω-conotoxin MVIIC and MVIID caused a 70% blockade. K+-evoked catecholamine secretory responses were not reduced by ω-conotoxin GVIA (1 μM). In contrast, at 1 μM both ω-conotoxin
MVIIC and MVIID reduced the exocytotic response by 70%. These data strengthen the previously established conclusion that Q-type
Ca2+ channels that contribute to the regulation of secretion and are sensitive to ω-conotoxins MVIIC and MVIID are present in
bovine chromaffin cells. These channels, however, seem to possess binding sites for ω-conotoxins MVIIC and MVIID whose characteristics
differ considerably from those described to occur in the brain; they might represent a subset of Q-type Ca2+ channels or an entirely new subtype of voltage-dependent high-threshold Ca2+ channel.
Received: 16 April 1997 / Received after revision: 10 July 1997 / Accepted: 23 July 1997 相似文献
86.
Anfinogenova YJ Baskakov MB Kovalev IV Kilin AA Dulin NO Orlov SN 《Pflügers Archiv : European journal of physiology》2004,449(1):42-55
This study elucidates the role of cell volume in contractions of endothelium-denuded vascular smooth muscle rings (VSMR) from the rat aorta. We observed that hyposmotic swelling as well as hyper- and isosmotic shrinkage led to VSMR contractions. Swelling-induced contractions were accompanied by activation of Ca2+ influx and were abolished by nifedipine and verapamil. In contrast, contractions of shrunken cells were insensitive to the presence of L-type channel inhibitors and occurred in the absence of Ca2+o. Thirty minutes preincubation with bumetanide, a potent Na+,K+,Cl– cotransport (NKCC) inhibitor, decreased Cl–i content, nifedipine-sensitive 45Ca uptake and contractions triggered by modest depolarization ([K+]o=36 mM). Elevation of [K+]o to 66 mM completely abolished the effect of bumetanide on these parameters. Bumetanide almost completely abrogated phenylephrine-induced contraction, partially suppressed contractions triggered by hyperosmotic shrinkage, but potentiated contractions of isosmotically shrunken VSMR. Our results suggest that bumetanide suppresses contraction of modestly depolarized cells via NKCC inhibition and Cl–i-mediated membrane hyperpolarization, whereas augmented contraction of isosmotically shrunken VSMR by bumetanide is a consequence of suppression of NKCC-mediated regulatory volume increase. The mechanism of bumetanide inhibition of contraction of phenylephrine-treated and hyperosmotically shrunken VSMR should be examined further. 相似文献
87.
G. I. Sandle F. McGlone R. J. Davies 《Pflügers Archiv : European journal of physiology》1988,412(1-2):172-182
Previous in vivo studies in rat and man indicate that chronic renal insufficiency leads to an increase in the capacity of the large intestine for K secretion. The present studies were performed in isolated rat distal colon with conventional and K-sensitive microelectrodes to determine the cellular basis for enhanced colonic K secretion after 70% nephrectomy. The data revealed that in animals fed a regular diet, nephrectomy had no effect on the Na or K conductance of the apical membrane, or the kinetics of the basolateral membrane Na-K pump, but intracellular K activity decreased from 70±4 mmol/l to 58±4 mmol/l (P<0.005). In control (non-nephrectomised) animals, feeding a diet modestly (4-fold) enriched with K resulted in small but significant increases in the Na and K conductance of the apical membrane, no change in the kinetics of the basolateral membrane Na-K pump, and a rise in intracellular K activity from 70±4 mmol/l to 94±7 mmol/l (P<0.005). In contrast, in animals fed the K enriched diet, nephrectomy resulted in (i) large, amiloride-sensitive increases in transepithelial voltage and total tissue conductance (consistent with an appreciable degree of secondary hyperaldosteronism), (ii) marked increases in the Na and K conductance of the apical membrane, (iii) significant hyperpolarisation of the basolateral membrane, (iv) a 100% increase (P<0.02) in the maximum activity of the basolateral membrane Na-K pump, and (v) a rise in intracellular K activity from 94±7 mmol/l to 129±7 mmol/l (P<0.0025). These data suggest that the combination of modest dietary K enrichment and 70% nephrectomy stimulated an active K secretory process which reflected an increase in the K excretory load applied to the colonic mucosa, and the effects of aldosterone. In this model of renal insufficiency, enhanced K secretion by the transcellular and paracellular (potential-dependent) pathways results in a marked rise in the K excretory capacity of the colon. 相似文献
88.
Armando A. Lagrutta Ke-Zhong Shen André Rivard R. Alan North J. P. Adelman 《Pflügers Archiv : European journal of physiology》1998,435(5):731-739
Structural determinants of permeation in large unit conductance calcium-activated potassium channels (BK channels) were investigated.
Y293 and F294 in the P-region of dSlo were substituted by tryptophans. Compared to wild-type channels, Y293W channels displayed reduced inward unitary currents
while F294W channels exhibited normal inward current amplitudes but flickery kinetics. Both mutations produced changes in
current/voltage relations under bi-ionic conditions. Sensitivity to block by external tetraethylammonium (TEA) was affected
in both channels, and the voltage dependence of TEA block was increased in F294W channels. Both mutations also affected gating
by shifting the half-maximal activation voltage of macroscopic conductance/voltage relations to more positive potentials,
and eliminating a slow component of deactivation. The double mutant did not produce ionic currents. These data are consistent
with a model in which Y293 contributes to a potassium-binding site close to the outer mouth of the dSlo pore, while F294 contributes to an energy barrier near this site.
Received: 16 September 1997 / Received after revision: 20 November 1997 / Accepted: 21 November 1997 相似文献
89.
Sarcolemmal K(ATP) channels in ageing 总被引:1,自引:0,他引:1
This review highlights some recent research addressing sarcolemmal K(ATP) channels in ageing. These channels are abundant in cardiac myocytes where they are essential in coupling the cellular metabolic state with membrane excitability. The opening of sarcolemmal ATP-sensitive K+ (K(ATP)) channels occurs during ischaemia and protect the heart against injury. Age-dependent changes in the myocardial susceptibility to ischemia have been observed in different species, including humans. Recent research has demonstrated that ageing is associated with decrease in numbers of sarcolemmal K(ATP) in hearts from females, but not males. This phenomenon seems to be associated with age-dependent decrease in concentration of circulating estrogens. In the heart, SUR2A, a regulatory subunit of K(ATP) channels, is present in excess over Kir6.2, a pore-forming K(ATP) channel subunit. The consequence of this is that SUR2A is a subunit that controls the number of sarcolemmal K(ATP) channels. Estrogens specifically up-regulate SUR2A and, thereby, control the number of sarcolemmal K(ATP) channels. Age-dependent loss of sarcolemmal K(ATP) channels creates a cardiac phenotype more sensitive to ischaemia, which may explain, at least in part, an ageing-associated decrease of myocardial tolerance to stress that occurs in elderly women. 相似文献
90.
Shevtzova EF Kireeva EG Bachurin SO 《Bulletin of experimental biology and medicine》2001,132(6):1173-1176
Beta-Amyloid peptide fragment 25-35 potentiated phosphate- and calcium-induced opening of mitochondrial channels and caused swelling of mitochondria (even without exogenous calcium and phosphate). These changes were accompanied by accumulation of lipid peroxidation products in mitochondria. Specific inhibitors of mitochondrial channels ADP and cyclosporine A prevented beta-amyloid peptide-induced swelling of mitochondria. Our findings suggest that potentiation of mitochondrial channel opening is an important component of the neurodegenerative effect of beta-amyloid. 相似文献