共查询到20条相似文献,搜索用时 31 毫秒
1.
H. Vais C. Rucareanu P. N. R. Usherwood 《Pflügers Archiv : European journal of physiology》1996,432(4):700-707
The plasma membrane of locust skeletal muscle contains two types of K+ channel; a maxi, Ca2+-activated 170 pS channel (BK channel) and an inward rectifier of 35 pS conductance (IK channel). The effects of ryanodine,
9, 21-didehydroryanodine and 9, 21-didehydroryanodol on these channels have been investigated. In the concentration domain
10−9 M to 10−5 M, ryanodine irreversibly induced a dose-dependent reduction of the reversal potential (V
rev) of the channel currents, measured under physiologically normal K+ and Na+ gradients, i.e. from ≈60 mV in the absence of ryanodine to ≈15 mV for 10−5 M ryanodine. The alteration of K+ channel selectivity was Ca2+ independent. 9, 21-Didehydroryanodine and 9, 21-didehydroryanodol reduced V
rev, but only to ≈35 mV during application of 10−5 M of these compounds. 9, 21-Didehydroryanodine also diminished the conductances of the locust K+ channels. The three ryanoids reduced V
rev of a Ca2+-activated, high-conductance channel in inside-out patches excised from mouse interosseal muscle, although the changes were
in each case less pronounced than those for the locust K+ channels. Also, the action of 9, 21-didehydroryanodine on mouse K+ (BK) channels was restricted to a shift of V
rev. For all three ryanoids, the IC50 coefficients (i.e. the concentration of toxin that gave a 50% reduction in V
rev) for the shifts in V
rev were similar for the locust and mouse muscle K+ channels.
Received: 12 June 1995/Received after revision and accepted: 30 January 1996 相似文献
2.
Falcao S Rousseau G Baroudi G Vermeulen M Bouchard C Jones DL Cardinal R 《Pflügers Archiv : European journal of physiology》2007,454(6):999-1009
To show that reductions in connexin43 (Cx43) can contribute, in association with electrophysiological alterations identified
from unipolar recordings, to conduction disturbances in a realistic model of heart failure, canines were subjected to chronic
rapid pacing (240/min for 4 weeks) and progressive occlusion of the left coronary circumflex artery (LCx) by an ameroid constrictor.
Alterations identified from 191 epicardial recordings included abrupt activation delay, functional block, ST segment potential
elevation, and reduced maximum negative slope (−dV/dt
max). The LCx territory was divided into apical areas with depressed conduction velocity (LCx1: 0.06 ± 0.04 m/s, mean ± SD) and
basal areas with relatively preserved conduction (LCx2: 0.28 ± 0.01 m/s). Subepicardial Cx43 immunoblot measurements (percent
of corresponding healthy heart measurements) were reduced in LCx1 (∼40%) and LCx2 (∼60%). In addition, −dV/dt
max was significantly depressed (−3.8 ± 3.3 mV/ms) and ST segment potential elevated (23.3 ± 14.6 mV) in LCx1 compared to LCx2
(−9.5 ± 3.4 mV/ms and 0.3 ± 1.4 mV). Anisotropic conduction, Cx43 and ST segment potential measurements from the left anterior
descending coronary artery territory, and interstitial collagen from all regions were similar to the healthy. Thus, moderate
Cx43 reduction to “clinically relevant” levels can, in conjunction with regional energetic stress and depression of sarcolemmal
active generator properties, provide a substrate for conduction disturbances. 相似文献
3.
J. P. Winpenny A. Harris M. A. Hollingsworth B. E. Argent M. A. Gray 《Pflügers Archiv : European journal of physiology》1998,435(6):796-803
Using the whole-cell patch-clamp technique, a calcium-activated chloride conductance (CACC) could be elicited in HPAF cells
by addition of 1 μM ionomycin to the bath solution (66 ± 22 pA/pF;V
m + 60 mV) or by addition of 1 μM calcium to the pipette solution (136 ± 17 pA/pF; V
m + 60 mV). Both conductances had similar biophysical characteristics, including time-dependent inactivation at hyperpolarising
potentials and a linear/slightly outwardly rectifying current/voltage (I/V) curve with a reversal potential (E
rev) close to the calculated cloride equilibrium potential. The anion permeability sequence obtained from shifts in E
rev was I > Br ≥ Cl. 4,4′-Diisothiocyanatostilbene disulphonic acid (DIDS, 500 μM) caused a 13% inhibition of the current (V
m + 60 mV) while 100 μM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 μM tamoxifen, all chloride channel blockers, had no
marked effects (8%, –6% and –2% inhibition respectively). Niflumic acid (100 μM) caused a voltage-dependent inhibition of
the current of 48% and 17% (V
m ± 60 mV, respectively). In freshly isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 μM calcium in the
pipette solution (260 ± 62 pA/pF; V
m + 60 mV). The presence of this CACC in human PDCs could provide a possible therapeutic pathway for treatment of pancreatic
insufficiency of the human pancreas in cystic fibrosis.
Received: 2 October 1997 / Received after revision: 28 November 1997 / Accepted: 1 December 1997 相似文献
4.
Kim SH Bae YM Sung DJ Park SW Woo NS Kim B Cho SI 《Pflügers Archiv : European journal of physiology》2007,454(6):891-902
Clinical doses of ketamine typically increase blood pressure, heart rate, and cardiac output. However, the precise mechanism
by which ketamine produces these cardiovascular effects remains unclear. The voltage-gated K+ (KV) channel is the major regulator of resting membrane potential (E
m) and vascular tone in many arteries. Therefore, we sought to evaluate the effects of ketamine on KV currents using the standard whole-cell patch clamp recordings in single myocytes, enzymatically dispersed from rat mesenteric
arteries. Ketamine [(±)-racemic mixture] inhibited KV currents reversibly and concentration dependently with a K
d
of 566.7 ± 32.3 μM and Hill coefficient of 0.75 ± 0.03. The inhibition of KV currents by ketamine was voltage independent, and the time courses of channel activation and inactivation were little affected.
The effects of ketamine on steady-state activation and inactivation curves were also minimal. Use-dependent inhibition was
not observed either. S(+)-ketamine inhibited KV currents with similar potency and efficacy as the racemic mixture. The average resting E
m in rat mesenteric artery myocytes was −44.1 ± 4.2 mV, and both racemic and S(+)-ketamine induced depolarization of E
m (15.8 ± 3.6 and 24.3 ± 5.0 mV at 100 μM, respectively). We conclude that ketamine induces E
m depolarization in vascular myocytes by blocking KV channels in a state-independent manner, which may contribute to the increased vascular tone and blood pressure produced by
this drug under a clinical setting. 相似文献
5.
Anderson WD Galván EJ Mauna JC Thiels E Barrionuevo G 《Pflügers Archiv : European journal of physiology》2011,462(6):895-912
The present study examines the biophysical properties and functional implications of I
h in hippocampal area CA3 interneurons with somata in strata radiatum and lacunosum-moleculare. Characterization studies showed a small maximum h-conductance (2.6 ± 0.3 nS, n = 11), shallow voltage dependence with a hyperpolarized half-maximal activation (V
1/2 = −91 mV), and kinetics characterized by double-exponential functions. The functional consequences of I
h were examined with regard to temporal summation and impedance measurements. For temporal summation experiments, 5-pulse mossy
fiber input trains were activated. Blocking I
h with 50 μM ZD7288 resulted in an increase in temporal summation, suggesting that I
h supports sensitivity of response amplitude to relative input timing. Impedance was assessed by applying sinusoidal current
commands. From impedance measurements, we found that I
h did not confer theta-band resonance, but flattened the impedance–frequency relations instead. Double immunolabeling for hyperpolarization-activated
cyclic nucleotide-gated proteins and glutamate decarboxylase 67 suggests that all four subunits are present in GABAergic interneurons
from the strata considered for electrophysiological studies. Finally, a model of I
h was employed in computational analyses to confirm and elaborate upon the contributions of I
h to impedance and temporal summation. 相似文献
6.
The effect of shear stress on the basolateral membrane potential of proximal convoluted tubule of the rat kidney 总被引:1,自引:0,他引:1
Lopardo ML Diaz-Sylvester P Amorena C 《Pflügers Archiv : European journal of physiology》2007,454(2):289-295
As consequence of glomerular filtration the viscosity of blood flowing through the efferent arteriole increases. Recently,
we found that shear stress modulates proximal bicarbonate reabsorption and nitric oxide (NO·) was the chemical mediator of
this effect. In the present work, we found that agonists of NO· production affected basolateral membrane potential (V
blm) of the proximal convoluted tubule (PCT) epithelium. Using paired micropuncture experiments, we perfused peritubular capillaries
with solutions with different viscosity while registering the V
blm. Our results showed that a 50% increment in the viscosity, or the addition of bradykinin (10−5 M) to the peritubular perfusion solution, induced a significant and similar hyperpolarization of the V
blm at the PCT epithelium of 6 ± 0.7 mV (p < 0.05). Both hyperpolarizations were reverted by l-NAME (10−4 M). Addition of 2,2′-(hydroxynitrosohydrazino) bis-ethanamine (NOC-18) 3 × 10−4 M to the peritubular perfusion solution induced a hyperpolarization of the same magnitude of that high viscosity or bradykinin.
These results strongly suggest the involvement of NO· in the effect of high viscosity solutions. This effect seems to be mediated
by activation of channels as glybenclamide (5 × 10−5 M) added to peritubular solutions induced a larger depolarization of the V
blm with high viscosity solutions. Acetazolamide (5 × 10−5 M) added to high viscosity solutions induced a larger hyperpolarization (8 ± 1 mV; p < 0.05), suggesting that depolarizing current due to exit across the basolateral membrane damps the hyperpolarizing effect of high viscosity. Considering that Na+ and consequently water reabsorption is highly dependent on electrical gradient, the present data suggest that the endothelium
of kidney vascular bed interacts in paracrine fashion with the epithelia, affecting V
blm and thus modulating PCT reabsorption. 相似文献
7.
Matos JE Sorensen MV Geyti CS Robaye B Boeynaems JM Leipziger J 《Pflügers Archiv : European journal of physiology》2007,454(6):977-987
Luminal P2 receptors are ubiquitously expressed in transporting epithelia. In steroid-sensitive epithelia (e.g., lung, distal
nephron) epithelial Na+ channel (ENaC)-mediated Na+ absorption is inhibited via luminal P2 receptors. In distal mouse colon, we have identified that both, a luminal P2Y2 and a luminal P2Y4 receptor, stimulate K+ secretion. In this study, we investigate the effect of luminal adenosine triphosphate/uridine triphosphate (ATP/UTP) on electrogenic
Na+ absorption in distal colonic mucosa of mice treated on a low Na+ diet for more than 2 weeks. Transepithelial electrical parameters were recorded in an Ussing chamber. Baseline parameters:
transepithelial voltage (V
te): −13.7 ± 1.9 mV (lumen negative), transepithelial resistance (R
te): 24.1 ± 1.8 Ω cm2, equivalent short circuit current (I
sc): −563.9 ± 63.8 μA/cm2 (n = 21). Amiloride completely inhibited I
sc to −0.5 ± 8.5 μA/cm2. Luminal ATP induced a slowly on-setting and persistent inhibition of the amiloride-sensitive I
sc by 160.7 ± 29.7 μA/cm2 (n = 12, NMRI mice). Luminal ATP and UTP were almost equipotent with IC50 values of 10 μM and 3 μM respectively. In P2Y2 knock-out (KO) mice, the effect of luminal UTP on amiloride-sensitve Na+ absorption was absent. In contrast, in P2Y4 KO mice the inhibitory effect of luminal UTP on Na+ absorption remained present. Semiquantitative polymerase chain reaction did not indicate regulation of the P2Y receptors
under low Na+ diet, but it revealed a pronounced axial expression of both receptors with highest abundance in surface epithelia. Thus,
luminal P2Y2 and P2Y4 receptors and ENaC channels co-localize in surface epithelium. Intriguingly, only the stimulation of the P2Y2 receptor mediates inhibition of electrogenic Na+ absorption. 相似文献
8.
Production and secretion of testosterone in Leydig cells are mainly controlled by the luteinizing hormone (LH). Biochemical
evidences suggest that the activity of Cl− ions can modulate the steroidogenic process, but the specific ion channels involved are not known. Here, we extend the characterization
of Cl− channels in mice Leydig cells (50–60 days old) by describing volume-activated Cl− currents (ICl,swell). The amplitude of ICl,swell is dependent on the osmotic gradient across the cell membrane, with an apparent EC50 of ∼75 mOsm. These currents display the typical biophysical signature of volume-activated anion channels (VRAC): dependence
on intracellular ATP, outward rectification, inactivation at positive potentials, and selectivity sequence (I− > Cl− > F−). Staurosporine (200 nM) did not block the activation of ICl,swell. The block induced by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB; 128 μM), SITS (200 μM), ATP (500 μM), pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate
(PPADS; 100 μM), and Suramin (10 μM) were described by the permeant blocker model with apparent dissociation constant at 0 mV
and fractional distance of the binding site (δ) of 334 μM and 47 %, 880 μM and 35 %, 2,100 μM and 49%, 188 μM and 27%, and 66.5 μM and 49%, respectively. These numbers
were derived from the peak value of the currents. We conclude that ICl,swell in Leydig cells are activated independently of purinergic stimulation, that Suramin and PPADS block these currents by a direct
interaction with VRAC and that ATP is able to permeate this channel. 相似文献
9.
We attempted to test whether the balance between muscular metabolic capacity and oxygen supply capacity in endurance-trained
athletes (ET) differs from that in a control group of normal physically active subjects by using exercises with different
muscle masses. We compared maximal exercise in nine ET subjects [Maximal oxygen uptake (VO2max) 64 ml kg−1 min−1 ± SD 4] and eight controls (VO2max 46 ± 4 ml kg−1 min−1) during one-legged knee extensions (1-KE), two-legged knee extensions (2-KE) and bicycling. Maximal values for power output
(P), VO2max, concentration of blood lactate ([La−]), ventilation (VE), heart rate (HR), and arterial oxygen saturation of haemoglobin (SpO2) were registered. P was 43 (2), 89 (3) and 298 (7) W (mean ± SE); and VO2max: 1,387 (80), 2,234 (113) and 4,115 (150) ml min−1) for controls in 1-KE, 2-KE and bicycling, respectively. The ET subjects achieved 126, 121 and 126% of the P of controls (p < 0.05) and 127, 124, and 117% of their VO2max (p < 0.05). HR and [La−] were similar for both groups during all modes of exercise, while VE in ET was 147 and 114% of controls during 1-KE and bicycling,
respectively. For mass-specific VO2max (VO2max divided by the calculated active muscle mass) during the different exercises, ET achieved 148, 141, and 150% of the controls’
values, respectively (p < 0.05). During bicycling, both groups achieved 37% of their mass-specific VO2 during 1-KE. Finally we conclude that ET subjects have the same utilization of the muscular metabolic capacity during whole
body exercise as active control subjects. 相似文献
10.
Park JK Kim YC Sim JH Choi MY Choi W Hwang KK Cho MC Kim KW Lim SW Lee SJ 《Pflügers Archiv : European journal of physiology》2007,454(2):307-319
Employing microfluorometric system and patch clamp technique in rabbit basilar arterial myocytes, regulation mechanisms of
vascular excitability were investigated by applying intracellular pH (pHi) changers such as sodium acetate (SA) and NH4Cl. Applications of caffeine produced transient phasic contractions in a reversible manner. These caffeine-induced contractions
were significantly enhanced by SA and suppressed by NH4Cl. Intracellular Ca2+ concentration ([Ca2+]i) was monitored in a single isolated myocyte and based the ratio of fluorescence using Fura-2 AM (R
340/380). SA (20 mM) increased and NH4Cl (20 mM) decreased R
340/380 by 0.2 ± 0.03 and 0.1 ± 0.02, respectively, in a reversible manner. Caffeine (10 mM) transiently increased R
340/380 by 0.9 ± 0.07, and the ratio increment was significantly enhanced by SA and suppressed by NH4Cl, implying that SA and NH4Cl may affect [Ca2+]i (p < 0.05). Accordingly, we studied the effects of SA and NH4Cl on Ca2+-activated K+ current (IKCa) under patch clamp technique. Caffeine produced transient outward current at holding potential (V
h) of 0 mV, caffeine induced transient outward K+ current, and the spontaneous transient outward currents were significantly enhanced by SA and suppressed by NH4Cl. In addition, IKCa was significantly increased by acidotic condition when pHi was lowered by altering the NH4Cl gradient across the cell membrane. Finally, the effects of SA and NH4Cl on the membrane excitability and basal tension were studied: Under current clamp mode, resting membrane potential (RMP)
was −28 ± 2.3 mV in a single cell level and was depolarized by 13 ± 2.4 mV with 2 mM tetraethylammonium (TEA). SA hyperpolarized
and NH4Cl depolarized RMP by 10 ± 1.9 and 16 ± 4.7 mV, respectively. SA-induced hyperpolarization and relaxation of basal tension
was significantly inhibited by TEA. These results suggest that SA and NH4Cl might regulate vascular tone by altering membrane excitability through modulation of [Ca2+]i and Ca2+-activated K channels in rabbit basilar artery. 相似文献
11.
Olufemi D. Owolabi 《Comparative clinical pathology》2011,20(2):163-172
Haematological and serum biochemical studies of natural population of Synodontis membranacea from Jebba Lake, North Central Nigeria were investigated in order to establish their mean and reference values. Bi-monthly
collection of 1,408 live fish samples was carried out between April 2002 and March 2004, using gill nets of various mesh sizes
ranging from 5.08 to 10.16 cm. The mean baseline value established for species-specific haematological and serum biochemical
parameters were red blood cell (RBC) 3.83 ± 1.49 × 1012 l−1, haemoglobin (HB) 8.38 ± 1.96 g dl−1, and packed cell volume (PCV) 25.65 ± 5.89%; mean cell volume 78.25 ± 37.90 fl; mean cell haemoglobin (MCH) 33.04 ± 12.50 pg;
mean cell haemoglobin concentration 26.53 ± 15.18 g dl−1; white blood cell (WBC) 315.65 ± 95.37 × 10−9; agranulocytes (Agr) 82.07 ± 11.38%; monocytes (Mon) 6.37 ± 3.01%; lymphocytes (Lym) 76.49 ± 10.81%; granulocytes (Gran)
40.28 ± 17.48%; neutrophils (Neut) 24.42 ± 10.68%; eosinophils (Eos) 16.14 ± 8.25%; basophils 0.09 ± 0.04%; protein 40.19 ± 7.45 g l−1; albumin 19.78 ± 5.67 g l−1; creatinine 49.71 ± 16.15 μmol l−1; urea 3.05 ± 0.67 nmol l−1; uric acid 0.76 ± 0.33 nmol l−1; glucose 4.24 ± 1.74 mmol l−1; cholesterol 8.46 ± 2.27 mmol l−1; calcium 2.35 ± 0.94 mmol l−1; potassium 13.36 ± 4.45 mmol l−1; sodium 139.39 ± 23.19 mmol l−1; alanine aminotransferase (ALT) 11.79 ± 2.67 U l−1; aspartate aminotransferase 16.80 ± 4.73 U l−1; and alkaline phosphatase 63.01 ± 20.44 U l−1. Only three of these parameters (i.e. neutrophil, glucose and potassium) differed significantly (P > 0.05) on gender basis. Pearson’s correlation coefficients indicated significant relationship of standard length and total
weight with RBC, PCV, HB, WBC, Agr, Mon, Lym, Gran, Neut, Eos, sodium, and ALT only. The study has provided baseline haematological
and biochemical data for use in health monitoring and productivity of S. membranacea, which would be of great value for future comparative surveys in this era of increased fish culture in Nigeria. 相似文献
12.
<Emphasis Type="Italic">V</Emphasis>O<Subscript>2</Subscript>max during successive maximal efforts 总被引:1,自引:0,他引:1
Foster C Kuffel E Bradley N Battista RA Wright G Porcari JP Lucia A deKoning JJ 《European journal of applied physiology》2007,102(1):67-72
The concept of VO2max has been a defining paradigm in exercise physiology for >75 years. Within the last decade, this concept has been both
challenged and defended. The purpose of this study was to test the concept of VO2max by comparing VO2 during a second exercise bout following a preliminary maximal effort exercise bout. The study had two parts. In Study #1,
physically active non-athletes performed incremental cycle exercise. After 1-min recovery, a second bout was performed at
a higher power output. In Study #2, competitive runners performed incremental treadmill exercise and, after 3-min recovery,
a second bout at a higher speed. In Study #1 the highest VO2 (bout 1 vs. bout 2) was not significantly different (3.95 ± 0.75 vs. 4.06 ± 0.75 l min−1). Maximal heart rate was not different (179 ± 14 vs. 180 ± 13 bpm) although maximal V
E was higher in the second bout (141 ± 36 vs. 151 ± 34 l min−1). In Study #2 the highest VO2 (bout 1 vs. bout 2) was not significantly different (4.09 ± 0.97 vs. 4.03 ± 1.16 l min−1), nor was maximal heart rate (184 + 6 vs. 181 ± 10 bpm) or maximal V
E (126 ± 29 vs. 126 ± 34 l min−1). The results support the concept that the highest VO2 during a maximal incremental exercise bout is unlikely to change during a subsequent exercise bout, despite higher muscular
power output. As such, the results support the “classical” view of VO2max. 相似文献
13.
Electrophysiological properties of the inward rectification of neurons in the rat suprachiasmatic nucleus (SCN) were examined
by using the single-electrode voltage-clamp method, in vitro. Inward rectifier current (I
H) was produced by hyperpolarizing step command potentials to membrane potentials negative to approximately −60 mV in nominally
zero-Ca2+ Krebs solution containing tetrodotoxin (1 μM), tetraethylammonium (40 mM), Cd2+ (500 μM) and 4-aminopyridine (1 mM).I
H developed during the hyperpolarizing step command potential with a duration of up to 5 s showing no inactivation with time.I
H was selectively blocked by extracellular Cs+ (1 mM). The activation of the H-channel conductance (G
H) ranged between −55 and −120 mV. TheG
H was 80–150 pS (n=4) at the half-activation voltage of −84±7 mV (n=4). The reversal potential ofI
H obtained by instantaneous current voltage (I/V) relations was −41±6mV (n=4); it shifted to −51±8mV (n=3) in low-Na+ (20 mM) solution and to −24±4 mV (n=4) in high-K+ (20 mM) solution. Forskolin (1–10 μM) produced an inward current and increased the amplitude ofI
H. Forskolin did not change the half-activation voltage ofG
H. 8-Bromo-adenosine 3′,5′-cyclic monophosphate (8-Br-cAMP, 0.1–1 mM) and dibutyryl-cAMP (0.1–1 mM) enhancedI
H. 3-Isobutyl-1-methylxanthine (IBMX, 1 mM) also enhancedI
H. The results suggest that the inward rectifier cation current is regulated by the basal activity of adenylate cyclase in
neurons of the rat SCN. 相似文献
14.
Differential contribution of TM6 and TM12 to the pore of CFTR identified by three sulfonylurea-based blockers 总被引:1,自引:0,他引:1
Cui G Song B Turki HW McCarty NA 《Pflügers Archiv : European journal of physiology》2012,463(3):405-418
Previous studies suggested that four transmembrane domains 5, 6, 11, 12 make the greatest contribution to forming the pore
of the CFTR chloride channel. We used excised, inside-out patches from oocytes expressing CFTR with alanine-scanning mutagenesis
in amino acids in TM6 and TM12 to probe CFTR pore structure with four blockers: glibenclamide (Glyb), glipizide (Glip), tolbutamide
(Tolb), and Meglitinide. Glyb and Glip blocked wildtype (WT)-CFTR in a voltage-, time-, and concentration-dependent manner.
At V
M = −120 mV with symmetrical 150 mM Cl− solution, fractional block of WT-CFTR by 50 μM Glyb and 200 μM Glip was 0.64 ± 0.03 (n = 7) and 0.48 ± 0.02 (n = 7), respectively. The major effects on block by Glyb and Glip were found with mutations at F337, S341, I344, M348, and
V350 of TM6. Under similar conditions, fractional block of WT-CFTR by 300 μM Tolb was 0.40 ± 0.04. Unlike Glyb, Glip, and
Meglitinide, block by Tolb lacked time-dependence (n = 7). We then tested the effects of alanine mutations in TM12 on block by Glyb and Glip; the major effects were found at
N1138, T1142, V1147, N1148, S1149, S1150, I1151, and D1152. From these experiments, we infer that amino acids F337, S341,
I344, M348, and V350 of TM6 face the pore when the channel is in the open state, while the amino acids of TM12 make less important
contributions to pore function. These data also suggest that the region between F337 and S341 forms the narrow part of the
CFTR pore. 相似文献
15.
Lai N Tolentino-Silva F Nasca MM Silva MA Gladden LB Cabrera ME 《European journal of applied physiology》2012,112(3):973-982
The effect of exercise intensity on the on- and off-transient kinetics of oxygen uptake (VO2) was investigated in African American (AA) and Caucasian (C) women. African American (n = 7) and Caucasian (n = 6) women of similar age, body mass index and weight, performed an incremental test and bouts of square-wave exercise at
moderate, heavy and very heavy intensities on a cycle ergometer. Gas exchange threshold (LTGE) was lower in AA (13.6 ± 2.3 mL kg−1 min−1) than C (18.6 ± 5.6 mL kg−1 min−1). The dynamic exercise and recovery VO2 responses were characterized by mathematical models. There were no significant differences in (1) peak oxygen uptake (VO2peak) between AA (28.5 ± 5 mL kg−1 min−1) and C (31.1 ± 6.6 mL kg−1 min−1) and (2) VO2 kinetics at any exercise intensity. At moderate exercise, the on- and off- VO2 kinetics was described by a monoexponential function with similar time constants τ
1,on (39.4 ± 12.5; 38.8 ± 15 s) and τ
1,off (52.7 ± 10.1; 40.7 ± 4.4 s) for AA and C, respectively. At heavy and very heavy exercise, the VO2 kinetics was described by a double-exponential function. The parameter values for heavy and very heavy exercise in the AA
group were, respectively: τ
1,on (47.0 ± 10.8; 44.3 ± 10 s), τ
2,on (289 ± 63; 219 ± 90 s), τ
1,off (45.9 ± 6.2; 50.7 ± 10 s), τ
2,off (259 ± 120; 243 ± 93 s) while in the C group were, respectively: τ
1,on (41 ± 12; 43.2 ± 15 s); τ
2, on (277 ± 81; 215 ± 36 s), τ
1,off (40.2 ± 3.4; 42.3 ± 7.2 s), τ
2,off (215 ± 133; 228 ± 64 s). The on- and off-transients were symmetrical with respect to model order and dependent on exercise
intensity regardless of race. Despite similar VO2 kinetics, LTGE and gain of the VO2 on-kinetics at moderate intensity were lower in AA than C. However, generalization to the African American and Caucasian
populations is constrained by the small subject numbers. 相似文献
16.
Almassy J Sztretye M Lukacs B Dienes B Szabo L Szentesi P Vassort G Csernoch L Jona I 《Pflügers Archiv : European journal of physiology》2008,457(1):171-183
The benzothiazepine derivative K-201 has been suggested as a potential therapeutic agent due to its antiarrhythmogenic action.
To understand how the drug alters calcium release from the sarcoplasmic reticulum (SR), we investigated its effects on the
SR calcium channel and calcium pump by single channel electrophysiology, whole-cell confocal microscopy, and ATPase activity
measurements on control and post-myocardial infarcted (PMI) rat skeletal muscle. In bilayers, K-201 induced two subconductance
states corresponding to ∼24% (S1) and ∼13% (S2) of the maximum conductance. Dependence of event frequency and of time spent in S1 and S2 on the drug concentration was biphasic both in control and in PMI rats, with a maximum at 50 μM. At this concentration, the
channel spends 26 ± 4% and 24 ± 4%, respectively, of the total time in these subconductance states at positive potentials,
while no subconductances are observed at negative potentials. K-201 altered the frequency of elementary calcium release events:
spark frequency decreased from 0.039 ± 0.001 to 0.023 ± 0.001 s−1 sarcomere−1, while the frequency of embers increased from 0.011 ± 0.001 to 0.023 ± 0.001 s−1 sarcomere−1. Embers with different amplitude levels were observed after the addition of the drug. K-201 inhibited the Ca2+ ATPase characterized by IC50,contr = 119 ± 21 μM and n
Hill,contr = 1.84 ± 0.48 for control and IC50,PMI = 122 ± 18 μM and n
Hill,PMI = 1.97 ± 0.24 for PMI animals. These results suggest that although K-201 would increase the appearance of subconductance
states, the overall calcium release is reduced by the drug. In addition, the effect of K-201 is identical on calcium release
channels from control and PMI rats. 相似文献
17.
18.
19.
Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts 总被引:1,自引:0,他引:1
Wagner M Goltz D Stucke C Schwoerer AP Ehmke H Volk T 《Pflügers Archiv : European journal of physiology》2007,454(4):595-604
Inhibition of endothelin-A (ETA) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study,
we investigate the effect of ETA-receptor inhibition on the development of regional alterations of the transient outward K+ current (I
to) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague–Dawley
rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ETA-receptor antagonist darusentan (LU135252, 35 mg [kg body weight]−1 day−1) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p < 0.001) and caused a significant reduction in I
to (at +40 mV) in epicardial myocytes (19.5 ± 1.2 pA pF−1, n = 32 vs 23.2 ± 1.2 pA pF−1, n = 35, p < 0.05). Darusentan further reduced I
to in AS (15.4 ± 1.3 pA pF−1, n = 37, p < 0.05) and sham-operated animals (19.8 ± 1.6 pA pF−1, n = 48, ns.). The effects of AS and darusentan on I
to were significant and independent as tested by two-way analysis of variance. I
to was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude
of I
to in the epicardial region of the left ventricle but that ETA-receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy. 相似文献
20.
M. Slawik A. Zdebik M. J. Hug D. Kerstan J. Leipziger R. Greger 《Pflügers Archiv : European journal of physiology》1996,432(1):112-120
Acetylcholine-controlled exocrine secretion by pancreatic acini has been explained by two hypotheses. One suggests that NaCl
secretion occurs by secondary active secretion as has been originally described for the rectal gland of Squalus acanthias. The other is based on a “push-pull” model whereby Cl− is extruded luminally and sequentially taken up basolaterally. In the former model Cl− uptake is coupled to Na+ and basolateral K+ conductances play a crucial role, in the latter model, Na+ uptake supposedly occurs via basolateral non-selective cation channels. The present whole-cell patch-clamp studies were designed
to further explore the conductive properties of rat pancreatic acini. Pilot studies in approximately 300 cells revealed that
viable cells usually had a membrane voltage (V
m) more hyperpolarized than −30 mV. In all further studies V
m had to meet this criterion. Under control conditions V
m was −49 ± 1 mV (n = 149). The fractional K+ conductance (f
K) was 0.13 ± 0.1 (n = 49). Carbachol (CCH, 0.5 μmol/l) depolarized to −19 ± 1.1 mV (n = 63) and increased the membrane conductance (G
m) by a factor of 2–3. In the seeming absence of Na+ [replacement by N-methyl-D-glucamine (NMDG+)] V
m hyperpolarized slowly to −59 ± 2 mV (n = 90) and CCH still induced depolarizations to −24 ± 2 mV (n = 34). The hyperpolarization induced by NMDG+ was accompanied by a fall in cytosolic pH by 0.4 units, and a very slow and slight increase in cytosolic Ca2+. f
K increased to 0.34. The effect of NMDG+ on V
m was mimicked by the acidifying agents propionate and acetate (10 mmol/l) added to the bath. The present study suggests that
f
K makes a substantial contribution to G
m under control conditions. The NMDG+ experiments indicate that the non- selective cation conductance contributes little to V
m in the presence of CCH. Hence the present data in rat pancreatic acinar cells do not support the push-pull model.
Received: 8 November 1995/Received after revision: 18 December 1995/Accepted: 3 January 1996 相似文献