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101.
Properties and regulation of chloride channels in cystic fibrosis and normal airway cells 总被引:4,自引:0,他引:4
Karl Kunzelmann Hermann Pavenstädt Rainer Greger 《Pflügers Archiv : European journal of physiology》1989,415(2):172-182
The present study examines the properties of Cl–channels in cultured respiratory cells of cystic fibrosis (CF) patients and normal (N) individuals. In excised membrane patches the conductances for CF and N Cl– channels were larger at positive as compared to negative clamp voltages (V
c): 74±2.6 (V
c > 0) and 47±2.0 pS (V
c < 0) for CF (n= 57) and 69±3.6 (V
c > 0) and 45±2.3 pS (V
c < 0) for N (n=35). The open probability (P
o) of the channel increased markedly with depolarization. Both the voltage dependence of the conductance and of P
o contribute to the outward rectification of the channel. The time histogram analysis reveals two open and two closed time constants. The selectivity of the channel was Cl–=Br– =I– > NO
3
–
gluconate. The channel was inhibited reversibly by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) at 10–7 mol/l to 10–5 mol/l. While Cl– channels were present in cell attached patches of N cells, they were absent in those of CF cells. The mean conductance for cell attached (N) Cl– channels was 76±3.2 pS for positive clamp voltages (V
c) and 46±3.9 pS for negative V
c (n=8). When the membrane patches were excised from CF cells Cl– currents appeared spontaneously (n=19). The immediate appearance (within 1 s) of Cl– channels after excision was observed at positive (n=6) as well as at negative clamp voltage (n=13). Excision activation of CF Cl– channels was observed at low (< 10–9 mol/l) or high (10–3 mol/l) calcium activities on the cytosolic side of the excised patch. Variation of the Ca+ activity (< 10–9–10–3 mol/l) or pH (6.5–8.5) on the cytosolic side exerted no effects on these Cl– channels. These results suggest that Cl– channels are present in the apical membrane of CF and N respiratory cells but they seem to be inhibited in intact CF cells. Excision of the patch and hence removal of the cytosolic inhibitor leads to an activation of Cl– channels. The Cl– channels in excised patches of N and CF cells have identical properties. 相似文献
102.
Yamazaki M Ohno-Shosaku T Fukaya M Kano M Watanabe M Sakimura K 《Neuroscience research》2004,50(4):369-374
Stargazin (γ-2) is disrupted in the ataxic and epileptic mutant mouse, stargazer (stg). The striking defect in the stg cerebellum is the lack of functional AMPA receptors on granule cells. Recently, it has been reported that γ-2 and its related molecules are crucial for the surface expression, synaptic targeting and recycling of AMPA receptors, being termed collectively as the transmembrane AMPA receptor regulatory proteins (TARPs). However, it is still unclear whether TARPs directly modulate AMPA receptor activity. Here we report that coexpression of GluR1 (GluR1) with γ-2 using HEK293 cells and Xenopus oocytes markedly enhanced glutamate-induced currents. This effect was far beyond the increase of AMPA receptor surface expression and accompanied by increased glutamate affinity and subunit cooperativity. Other member of TARPs (γ-3, γ-4, and γ-8) also enhanced the current response through the AMPA receptors. The enhancing effect by γ-2 coexpression was further observed for homomeric GluR2 (GluR2) channels, which, when expressed alone, are known to produce only a small or negligible current response. These results suggest that γ-2 not only promotes AMPA receptor surface expression but also directly modulates AMPA receptor activity. 相似文献
103.
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
104.
Ken Nakazawa Kazuhide Inoue Kannosuke Fujimori Akira Takanaka 《Pflügers Archiv : European journal of physiology》1991,418(3):214-219
The effects of suramin, reactive blue 2 (RB2) and d-tubocurarine (d-TC) were investigated electrophysiologically to elucidate the mechanisms underlying their antagonism of P2 purinoceptor-mediated responses. All three compounds inhibited an adenosine triphosphate (ATP)-activated inward current in rat phaeochromocytoma PC12 cells in a concentration-dependent manner. The order of potency was RB2 > suramin > d-TC. The inhibition induced by suramin or RB2 was reversible, whereas that induced by d-TC was not reversed after a 5-min rinse. The inactivation of the ATP-activated current was accelerated by d-TC but not by suramin or RB2. RB2 administered simultaneously with ATP exerted much weaker inhibition compared to that induced by prior administration, suggesting that RB2 is a slowly acting antagonist. This was not observed for suramin or d-TC. Suramin and RB2 caused a parallel shift in the concentration/response curve for the ATP-activated current. With d-TC the maximal response of ATP was decreased but the concentration producing half-maximal response was unchanged. The voltage dependency of the ATP-activated current showed less inward rectification in the presence of d-TC. Suramin or RB2 did not affect the voltage dependency. These results suggest that suramin and RB2 reversibly block binding of ATP to receptors, whereas d-TC blocks ion permeability through the ATP-activated channel. 相似文献
105.
Contreras X Bennasser Y Chazal N Moreau M Leclerc C Tkaczuk J Bahraoui E 《Virology》2005,332(1):316-328
HIV-1 Tat protein, acting at the cell membrane, stimulates the production by human monocytes of TNF-α, a cytokine implicated in both HIV-1 replication and pathogenesis. Here, we analyze, in primary human monocytes, the mechanisms involved in Tat-stimulated calcium mobilization and its relationship with TNF-α production. We show that the Tat protein induces a calcium signal by mobilizing calcium from extracellular stores. This calcium signal is totally blocked when cells are stimulated in the presence of DHP receptor inhibitors such as nimodipine or calcicludine, thus suggesting the implication of this L-type calcium channel. By using RT-PCR amplification, Western blot with antibodies directed against the α1D subunit, binding assays with specific agonists or antagonists, and inhibition with specific antisense oligonucleotides, we show that DHP receptors are expressed and functional in primary human monocytes. Interestingly, we demonstrate that Tat-induced calcium mobilization is tightly linked to TNF-α production, thus indicating that Tat-induced mobilization and TNF-α production are entirely mediated by DHP receptors, as shown by their total inhibition by nimodipine, calcicludine, or anti-α1D antisense oligonucleotides. 相似文献
106.
《Immunity》2020,52(4):683-699.e11
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107.
We studied the effect of the nitric oxide (NO) donor, sodium nitroprusside (SNP), on the macroscopic and single-channel currents
due to the 22-pS Ca2+ channel in smooth muscle cells from guinea pig basilar artery. In nystatin-perforated whole-cell recordings, 50 nM SNP decreased
the macroscopic current to 63±12% of control values, without changing the voltage dependence of the current. In cell-attached
patches with BAY-K8644 in the pipette, SNP caused a comparable decrease in single-channel availability (n ·P
o) that was dose dependent over the range of 10 nM to 10 μM SNP. SNP had no effect on single-channel properties, including
slope conductance, voltage dependence of activation, the number of open states, the time constants of the open states, and
the proportion of time spent in each open state. The effect of SNP (50 nM) on single Ca2+ channel openings was reproduced by 8-Br-cGMP (100 μM), which also reduced channel availability without altering channel properties.
The protein kinase inhibitor H-8 (1.5 μM), which exhibits relative specificity for cGMP-dependent protein kinase, completely
inhibited the decrease in single-channel availability expected with SNP. The dose-dependent decrease in Ca2+ channel availability caused by SNP was not altered by prior application of 8-Br-cAMP or forskolin, both of which cause an
increase in Ca2+ channel availability in these cells. Our findings suggest that NO decreases openings of Ca2+ channels in basilar artery smooth muscle cells without altering channel properties, and that it does so by a mechanism likely
to involve cGMP-dependent protein kinase.
Received: 2 July 1996 / Received after revision: 30 September 1996 / Accepted: 2 October 1996 相似文献
108.
Effects of cGMP-dependent phosphorylation on rat and human connexin43 gap junction channels 总被引:6,自引:0,他引:6
Brenda R. Kwak Juan C. Sáez Ronald Wilders Marc Chanson Glenn I. Fishman Elliot L. Hertzberg David C. Spray Habo J. Jongsma 《Pflügers Archiv : European journal of physiology》1995,430(5):770-778
The effects of 8-bromoguanosine 3:5-cyclic monophosphate (8Br-cGMP), a membrane-permeant activator of protein kinase G (PKG), were studied on rat and human connexin43 (Cx43), the most abundant gap junction protein in mammalian heart, which were exogenously expressed in SKHep1 cells. Under dual whole-cell voltage-clamp conditions, 8Br-cGMP decreased gap junctional conductance (gj) in rat Cx43-transfected cells by 24.0±3.7% (mean±SEM, n=5), whereas gj was not affected in human Cx43-transfected cells by the same treatment. The relaxation of gj in response to steps in transjunctional voltage observed in rat Cx43 transfectants was best fitted with three exponentials. Time constants and amplitudes of the decay phases changed in the presence of 8Br-cGMP. Single rat and human Cx43 gap junction channels were resolved in the presence of halothane. Under control conditions, three single-channel conductance states (j) of about 20, 40–45 and 70 pS were detected, the events of the intermediate size being most frequently observed. In the presence of 8Br-cGMP, the
j distribution shifted to the lower size in rat Cx43 but not in human Cx43 transfectants. Immunoblot analyses of Cx43 in subconfluent cultures of rat Cx43 or human Cx43 transfectants showed that 8Br-cGMP did not induce changes in the electrophoretic mobility of Cx43 in either species. However, the basal incorporation of [32P] into rat Cx43 was significantly altered by 8Br-cGMP, whereas this incorporation of [32P] into human Cx43 was not affected. We conclude that 8Br-cGMP modulates phosphorylation of rat Cx43 in SKHep1 cells, but not of human Cx43. This cGMP-dependent phosphorylation of rat Cx43 is associated with a decreased gj, which results from both an increase in the relative frequency of the lowest conductance state and a change in the kinetics of these channels. 相似文献
109.
C. P. Webb S. A. Greenfield 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1992,89(1):49-58
Summary Within the substantia nigra acetylcholinesterase has non-cholinergic actions that can be demonstrated at both behavioural and cellular levels: the aim of this study was, thus, to explore, in the in vitro guinea pig substantia nigra, the ionic mechanisms which mediate these non-classical phenomena. Acetylcholinesterase had a reversible hyperpolarizing action, via an opening of potassium channels, on a selective population of nigral neurons. These neurons could be identified by an ability to generate bursts of action potentials and by a sensitivity to either amphetamine or to a reduction of glucose in the perfusing medium. The acetylcholinesterase-induced hyperpolarization could not be attributed to a contaminant in the exogenous solution, since a highly purified preparation was even more potent. Furthermore, enzymatic action of any kind could be eliminated as boiled acetylcholinesterase was equally efficacious. The effect of acetylcholinesterase was not subject to tachyphylaxis and was resistant to blockade of potassium channels with tetraethylammonium: since both these phenomena are features of the D2 autoreceptor for dopamine within the substantia nigra, it seems unlikely that acetylcholinesterase is operating on the same target as dendritically released local dopamine. On the other hand, the actions of acetylcholinesterase were enhanced by low glucose and blocked by the sulfonylurea, tolbutamide. These results strongly suggest that acetylcholinesterase can exert a nonenzymatic action and that this action, in the substantia nigra, is mediated by an ATP-sensitive potassium channel. 相似文献
110.
Yoshihisa Kurachi Toshiaki Nakajima Tsuneaki Sugimoto 《Pflügers Archiv : European journal of physiology》1987,410(3):227-233
The short-term desensitization of the acetylcholine (ACh)-induced K+ channel current was examined in single atrial cells of guinea-pig heart. The tight-seal whole cell voltage clamp technique was used. The solution in the pipettes contained GTP or guanosine-5-O-(3-thiotriphosphate) (GTP-S, a non-hydrolyzable GTP analogue). In GTP-loaded cells, ACh evoked a specific K+ channel current via GTP-binding proteins (G) in a dose-dependent manner. The K+ current showed agonist-dependent desensitization similar to those reported in other cardiac tissues (Nilius 1983; Carmeliet and Mubagwa 1986). The cellular response to ACh was also desensitized by activation of P1-purinergic receptors with adenosine (Ado). In GTP-S-loaded cells, the K+ current was gradually induced even in the absence of agonists, probably due to direct activation of G proteins by GTP-S. In the early phase of the spontaneous current increase, ACh evoked a large current transiently. As the GTP-S-induced activation of the current progressed, the magnitude of the ACh-evoked current transient became smaller and finally negligible. Similar results were obtained when Ado was used as an agonist instead of ACh to induce the K+ current. Therefore, it is indicated that the agonistreceptor interaction may not be essential for the desensitization of ACh-induced K+ current in atrial myocytes. 相似文献