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131.
Previous studies in our laboratory have shown that Na absorption across the porcine endometrium is stimulated by PGF2α and cAMP-dependent activation of a barium-sensitive K channel located in the basolateral membrane of surface epithelial cells.
In this study, we identify and characterize this basolateral, barium-sensitive K conductance. Porcine uterine tissues were
mounted in Ussing chambers and bathed with KMeSO4 Ringer solution. Amphotericin B (70 μm) was added to the luminal solution to permeabilize the apical membrane and determine the current-voltage relationship of
the basolateral K conductance after activation by 100 μm CPT-cAMP. An inwardly rectifying current was identified which possessed a reversal potential of −53 mV when standard Ringer
solution was used to bathe the serosal surface. The K:Na selectivity ratio was calculated to be 12:1. Administration of 5
mm barium to the serosal solution completely inhibited the current activated by cAMP under these conditions. In addition to
these experiments, amphotericin-perforated whole cell patch clamp recordings were obtained from primary cultures of porcine
surface endometrial cells. The isolated cells displayed an inwardly rectifying current under basal conditions. This current
was significantly stimulated by CPT-cAMP and blocked by barium. These results together with our previous studies demonstrate
that cAMP increases Na absorption in porcine endometrial epithelial cells by activating an inwardly rectifying K channel present
in the basolateral membrane. Similar patch clamp experiments were conducted using cells from a human endometrial epithelial
cell line, RL95-2. An inwardly rectifying current was also identified in these cells which possessed a reversal potential
of −56 mV when the cells were bathed in standard Ringer solution. This current was blocked by barium as well as cesium. However,
the current from the human cells did not appear to be activated by cAMP, indicating that distinct subtypes of inwardly rectifying
K channels are present in endometrial epithelial cells from different species.
Received: 6 February 1997/Revised: 10 July 1997 相似文献
132.
The effects of the calmodulin antagonists W-7 and trifluoperazine have been measured on the Ca2+-activated potassium channel in the membrane surrounding protoplasmic drops expressed from internodal cells of charophyte
plants. The large-conductance (170 pS), voltage- and Ca2+-dependent gating, and prominent conductance substrate of this channel shows a strong kinetic resemblance to those of the
Maxi-K channel from animal cells.
This is the first study of the action of calmodulin antagonists which measures their effects on the most populated substates
as well as the closed and main open states of Maxi-K channels. The substate analysis provides new evidence for different modes
of action of- and different bindings sites for these calmodulin antagonists.
Neither antagonist produces the simple closure of the channel reported previously as its effect on the Maxi-K channel, though
both do induce flicker-block, reducing the mean current to near zero at high concentrations following an inverted Michaelis-Menten
curve.
W-7 reduces residence time in the fully open state, thus raising, in the same proportions, the probabilities of finding the
channel in the closed state or a pre-existing substate. Its binding to the channel is voltage- and calcium-dependent.
In contrast, trifluoperazine reduces residence in the open state and promotes an apparently new substate which overlaps the
closed state at −50 mV but is distinguishable from it at voltages more negative than −100 mV. This substate may represent
times that trifluoperazine is bound to the channel.
Both antagonists have effects clearly distinguishable from that of withdrawing calcium from the channel, which does not affect
open state residence time but increases closed state residence time. Thus neither antagonist reverses the activating effect
of Ca2−. This is good kinetic evidence against the view that the channel is activated by Ca2+-calmodulin and that the effect of a calmodulin antagonist is to reverse this process by making Ca2−-calmodulin less available.
Received: 26 August 1996/Revised: 7 October 1996 相似文献
133.
The gating and conduction properties of a channel activated by intracellular Na+ were studied by recording unitary currents in inside-out patches excised from lobster olfactory receptor neurons. Channel
openings to a single conductance level of 104 pS occurred in bursts. The open probability of the channel increased with increasing
concentrations of Na+. At 210 mm Na+, membrane depolarization increased the open probability e-fold per 36.6 mV. The distribution of channel open times could
be fit by a single exponential with a time constant of 4.09 msec at −60 mV and 90 mm Na+. The open time constant was not affected by the concentration of Na+, but was increased by membrane depolarization. At 180 mm Na+ and −60 mV, the distribution of channel closed times could be fit by the sum of four exponentials with time constants of
0.20, 1.46, 8.92 and 69.9 msec, respectively. The three longer time constants decreased, while the shortest time constant
did not vary with the concentration of Na+. Membrane depolarization decreased all four closed time constants. Burst duration was unaffected by the concentration of
Na+, but was increased by membrane depolarization. Permeability for monovalent cations relative to that of Na+ (P
X
/P
Na
), calculated from the reversal potential, was: Li+ (1.11) > Na+ (1.0) > K+ (0.54) > Rb+ (0.36) > Cs+ (0.20). Extracellular divalent cations (10 mm) blocked the inward Na+ current at −60 mV according to the following sequence: Mn2+ > Ca2+ > Sr2+ > Mg2+ > Ba2+. Relative permeabilities for divalent cations (P
Y
/P
Na
) were Ca2+ (39.0) > Mg2+ (34.1) > Mn2+ (15.5) > Ba2+ (13.8) > Na+ (1.0). Both the reversal potential and the conductance determined in divalent cation-free mixtures of Na+ and Cs+ or Li+ were monotonic functions of the mole fraction, suggesting that the channel is a single-ion pore that behaves as a multi-ion
pore when the current is carried exclusively by divalent cations. The properties of the channel are consistent with the channel
playing a role in odor activation of these primary receptor neurons.
Received: 17 September 1996/Revised: 15 November 1996 相似文献
134.
The yeast Peptide Sensitive Channel (PSC), a cationic channel of the mitochondrial outer membrane closes with slow kinetics
at potentials of either polarity. The properties of this inactivation closely resemble those of the Voltage-Dependent Anion
Channel (VDAC) slow kinetics closures. Addition of trypsin to one compartment suppresses the inactivation observed when this
compartment is made positive, but does not affect the inactivation observed at potentials of reverse polarity. Both sides
of the channel are sensitive. The reduced form of the Mast Cell Degranulating peptide (rMCD) increases the rate of inactivation,
but only when the polarity of the compartment to which it is added is positive. The effect is not reversed by washing the
peptide out, but is suppressed by trypsin. The peptide can bind to both sides of the membrane. The effect of rMCD on PSC closely
resembles that of the ``modulator' on VDAC. The similarities between PSC and VDAC suggest that the former might be a cationic
porin of the mitochondrial outer membrane possessing a structure closely related to that of VDAC.
Received: 2 February 1996/Revised: 18 October 1996 相似文献
135.
The effect of ethanol on maxi Ca2+-activated K+ channels (BK channels) in GH3 pituitary tumor cells was investigated using single-channel recordings and focusing on intracellular
signal transduction. In outside-out patches, ethanol caused a transient concentration-dependent increase of BK-channel activity.
30 mm (1.4‰) ethanol significantly increased mean channel open time and channel open probability by 26.3 ± 9% and 78.8 ± 10%, respectively;
single-channel current amplitude was not affected by ethanol. The augmenting effect of ethanol was blocked in the presence
of protein kinase C (PKC) inhibitors staurosporine, bisindolylmaleimide, and PKC (19–31) pseudosubstrate inhibitor as well
as by AMP-PNP (5′-adenylylimidodiphosphate), a nonhydrolyzable ATP-analogue, but not by the phospholipase C blocker U-73122.
Phosphatase inhibitors microcystin-LR and okadaic acid promoted the ethanol effect. The blocking effect was released at higher
concentrations of ethanol (100 mm) suggesting a second site of action or a competition between blockers and ethanol. Our results suggest that the effect of
ethanol on BK-channels is mediated by PKC stimulation and phosphorylation of the channels which increases channel activity
and hence may influence action potentials duration and hormone secretion.
Received: 24 July 1996/Revised: 27 December 1996 相似文献
136.
Protein Phosphorylation and Calcium Uptake into Rat Forebrain Synaptosomes: Modulation by the σ Ligand, 1,3-Ditolylguanidine 总被引:1,自引:0,他引:1
Paul J. Brent Lynn Herd Heather Saunders Alistair T. R. Sim Peter R. Dunkley 《Journal of neurochemistry》1997,68(5):2201-2211
Abstract: The σ ligand 1,3-di- O -tolylguanidine (DTG) increased basal dynamin and decreased depolarization-stimulated phosphorylation of the synaptosomal protein synapsin Ib without having direct effects on protein kinases or protein phosphatases. DTG dose-dependently decreased the basal cytosolic free Ca2+ concentration ([Ca2+ ]i ) and blocked the depolarization-dependent increases in [Ca2+ ]i . These effects were inhibited by the σ antagonists rimcazole and BMY14802. The nitric oxide donors sodium nitroprusside (SNP) and 8-( p -chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate decreased basal [Ca2+ ]i and the KCl-evoked rise in [Ca2+ ]i to an extent similar to DTG. SNP, but not DTG, produced a rise in cyclic GMP levels, suggesting that the effect of DTG on [Ca2+ ]i was not mediated via downstream regulation of cyclic GMP levels. DTG increased 45 Ca2+ uptake and efflux under basal conditions and inhibited the 45 Ca2+ uptake induced by depolarization with KCl. The KCl-evoked rise in [Ca2+ ]i was inhibited by ω-conotoxin (ω-CgTx)-GVIA and -MVIIC but not nifedipine and ω-agatoxin-IVA. The effect of DTG on decreasing the KCl-evoked rise in [Ca2+ ]i was additive with ω-CgTx-MVIIC but not with ω-CgTx-GVIA. These data suggest that DTG was producing some of its effects on synapsin I and dynamin phosphorylation and intrasynaptosomal Ca2+ levels via inhibition of N-type Ca2+ channels. 相似文献
137.
Abstract: Mutations in the unc-9 gene of the nematode Caenorhabditis elegans cause abnormal forward locomotion and an egg-retention phenotype. unc-9 mutations also reduce the worms' sensitivity to avermectin and block a form of hypersensitivity to volatile anesthetics. We report here the cloning and molecular characterization of unc-9 and show that it encodes a member of the OPUS family of proteins that is 56% identical to another OPUS protein, UNC-7. It is significant that unc-9 mutants share all phenotypes with unc-7 mutants. Mutants in another gene, unc-124 , also share all tested phenotypes with unc-9 mutants, including identical locomotory and egg-laying defects, suggesting that multiple genes are required for the same biochemical function. OPUS proteins are implicated in the function of invertebrate gap junctions, and, based on a new alignment including 24 members from C. elegans , we present a refined model for the structure of OPUS proteins suggesting that oligomers could form a hydrophilic pore. We also show that alteration of highly conserved proline residues in UNC-9 leads to a cold sensitivity that likely affects a step in protein expression rather than function. Finally, we speculate on the basis of the avermectin resistance and anesthetic response phenotypes. 相似文献
138.
139.
140.
B. Pittendrigh R. Reenan R. H. ffrench-Constant B. Ganetzky 《Molecular & general genetics : MGG》1997,256(6):602-610
The gene para in Drosophila melanogaster encodes an α subunit of voltage-activated sodium channels, the presumed site of action of DDT and pyrethroid insecticides.
We used an existing collection of Drosophila para mutants to examine the molecular basis of target-site resistance to pyrethroids and DDT. Six out of thirteen mutants tested
were associated with a largely dominant, 10- to 30-fold increase in DDT resistance. The amino acid lesions associated with
these alleles defined four sites in the sodium channel polypeptide where a mutational change can cause resistance: within
the intracellular loop between S4 and S5 in homology domains I and III, within the pore region of homology domain III, and
within S6 in homology domain III. Some of these sites are analogous with those defined by knockdown resistance (kdr) and super-kdr resistance-associated mutations in houseflies and other insects, but are located in different homologous units of the channel
polypeptide. We find a striking synergism in resistance levels with particular heterozygous combinations of para alleles that appears to mimic the super-kdr double mutant housefly phenotype. Our results indicate that the alleles analyzed from natural populations represent only
a subset of mutations that can confer resistance. The implications for the binding site of pyrethroids and mechanisms of target-site
insensitivity are discussed.
Received: 9 May 1997 / Accepted: 21 July 1997 相似文献