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1.
N. A. Popov 《Plasma Physics Reports》2003,29(8):695-708
A self-consistent model is constructed that makes it possible to investigate the formation of a leader channel in air and the evolution of the channel parameters in the developed stage, when the leader is as long as several meters or more. The initial stage of the formation of the channel is characterized by a rapid increase in the electron density and gas temperature, which is a consequence of the onset of thermal-ionizational instability. The radius of a fully developed plasma column at the current I=1 A in air at atmospheric pressure is R h?10?2 cm. Then, because of the gas-dynamic and thermal expansion, the plasma radius R h increases considerably; as a result, the electric field and the reduced field E/N in the corresponding parts of the channel decrease. In the case under consideration, the field in the “oldest” parts of the leader drops to 200 V/cm and even lower and the reduced field becomes as weak as E/N≤10 Td. In this case, the densities of the main species of neutral and charged particles at the center of the channel remain close to their thermodynamically equilibrium values. The results of calculations are compared with the available experimental data. 相似文献
2.
Kukita F 《The Journal of membrane biology》2011,242(3):119-135
In hypertonic solutions made by adding nonelectrolytes, K+ channels of squid giant axons opened at usual asymmetrical K+ concentrations in two different time courses; an initial instantaneous activation (I
IN) and a sigmoidal activation typical of a delayed rectifier K+ channel (I
D). The current–voltage relation curve for I
IN was fitted well with Goldman equation described with a periaxonal K+ concentration at the membrane potential above −10 mV. Using the activation–voltage curve obtained from tail currents, K+ channels for I
IN are confirmed to activate at the membrane potential that is lower by 50 mV than those for I
D. Both I
IN and I
D closed similarly at the holding potential below −100 mV. The logarithm of I
IN/I
D was linearly related with the osmolarity for various nonelectrolytes. Solute inaccessible volumes obtained from the slope
increased with the nonelectrolyte size from 15 to 85 water molecules. K+ channels representing I
D were blocked by open channel blocker tetra-butyl ammonium (TBA) more efficiently than in the absence of I
IN, which was explained by the mechanism that K+ channels for I
D were first converted to those for I
IN by the osmotic pressure and then blocked. So K+ channels for I
IN were suggested to be derived from the delayed rectifier K+ channels. Therefore, the osmotic pressure is suggested to exert delayed-rectifier K+ channels to open in shrinking rather hydrophilic flexible parts outside the pore than the pore itself, which is compatible
with the recent structure of open K+ channel pore. 相似文献
3.
Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart. The objective of this study
was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+]i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca2+ overload. The [Ca2+]i was clamped to either a controlled (65–100 nmol L−1) or increased (1 μmol L−1) level. The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques. We
found that the acute increase in [Ca2+]i shortened the action potential duration, reduced the action potential amplitude, maximum depolarization velocity and resting
membrane potential, caused delayed after-depolarizations (DADs), and triggered activity—compared with these parameters in
the control. The increased [Ca2+]i augmented late I
Na in a time-dependent manner, reduced I
CaL and I
K1, and increased I
Kr but not I
Ks. The results of this study can be used to explain calcium overload-induced ventricular arrhythmias. 相似文献
4.
Despite the progress in studies of the properties and functions of low-threshold calcium channels (LTCCs) [1], the mechanisms
of their selectivity and permeability remain unstudied in detail. We performed a comparative analysis of the selectivity of
three cloned pore-forming LTCC subunits (α1G, α1H, and α1I) functionally expressed in Xenopus oocytes with respect to bivalent alkaline-earth metal cations (Ba2+, Ca2+, and Sr2+. The relative conductivities (G) of these channels were determined according to the amplitudes of macroscopic currents (I) and potentials of zero currents (E). The currents were recorded after preliminary intracellular injection of a fast calcium buffer, BAPTA, in order to suppress
the endogenous calcium-dependent chloride conductivity. Channels formed by α1G subunits demonstrated the following ratios
of the amplitudes of macroscopic currents and potentials of zero current: I
Ca:I
Ba:I
Sr = 1.00:0.75:1.12 and E
Ca ≈ E
Ba ≈ E
Sr. For channels that were formed by α1H and α1I subunits, these ratios were as follows: I
Ca:I
Ba:I
Sr = 1.00:1.20:1.17, E
Ca ≈ E
Ba ≈ E
Sr and I
Ca:I
Ba:I
Sr = 1.00:1.48: 1.45, E
Ca ≈ E
Ba ≈ E
Sr respectively. The different macroscopic conductivities and similar potentials of zero current typical of α1G and α1I channels
indicate that, probably, various bivalent cations can in a differential manner influence the stochastic parameters of functioning
of these channels. At the same time, channels formed by α1H subunits are characterized by more positive potentials of zero
current for Ca2+. It seems possible that the selectivity of the above channels is determined by mechanisms that mediate the selectivity of
most high-threshold calcium channels (more affine binding of Ca2+ inside the pore).
Neirofiziologiya/Neurophysiology, Vol. 37, No. 4, pp. 319–329, July–August, 2005. 相似文献
5.
A three-dimensional radiative gas-dynamic model is applied to calculating the parameters of a continuous optical discharge
in crossed CO2 laser beams in air at atmospheric pressure.
__________
Translated from Fizika Plazmy, Vol. 26, No. 7, 2000, pp. 658–661.
Original Russian Text Copyright ¢ 2000 by Kulumbaev, Lelevkin. 相似文献
6.
T.E. DeCoursey S.Y. Kim M.R. Silver F.N. Quandt 《The Journal of membrane biology》1996,152(2):141-157
Ion channel expression was studied in THP-1 human monocytic leukemia cells induced to differentiate into macrophage-like cells
by exposure to the phorbol ester, phorbol 12-myristate 13-acetate (PMA). Inactivating delayed rectifier K+ currents, I
DR, present in almost all undifferentiated THP-1 monocytes, were absent from PMA-differentiated macrophages. Two K+ channels were observed in THP-1 cells only after differentiation into macrophages, an inwardly rectifying K+ channel (I
IR) and a Ca2+-activated maxi-K channel (I
BK). I
IR was a classical inward rectifier, conducting large inward currents negative to E
K and very small outward currents. I
IR was blocked in a voltage-dependent manner by Cs+, Na+, and Ba2+, block increasing with hyperpolarization. Block by Na+ and Ba2+ was time-dependent, whereas Cs+ block was too fast to resolve. Rb+ was sparingly permeant. In cell-attached patches with high [K+] in the pipette, the single I
IR channel conductance was ∼30 pS and no outward current could be detected. I
BK channels were observed in cell-attached or inside-out patches and in whole-cell configuration. In cell-attached patches the
conductance was ∼200–250 pS and at potentials positive to ∼100 mV a negative slope conductance of the unitary current was
observed, suggesting block by intracellular Na+. I
BK was activated at large positive potentials in cell-attached patches; in inside-out patches the voltage-activation relationship
was shifted to more negative potentials by increased [Ca2+]. Macroscopic I
BK was blocked by external TEA+ with half block at 0.35 mm. THP-1 cells were found to contain mRNA for Kv1.3 and IRK1. Levels of mRNA coding for these K+ channels were studied by competitive PCR (polymerase chain reaction), and were found to change upon differentiation in the
same direction as did channel expression: IRK1 mRNA increased at least 5-fold, and Kv1.3 mRNA decreased on average 7-fold.
Possible functional correlates of the changes in ion channel expression during differentiation of THP-1 cells are discussed.
Received: 19 September 1995/Revised: 14 March 1996 相似文献
7.
S. I. Tkachenko A. R. Mingaleev V. M. Romanova A. E. Ter-Oganes’yan T. A. Shelkovenko S. A. Pikuz 《Plasma Physics Reports》2009,35(9):734-753
Distribution of matter in the discharge channel formed upon a nanosecond electrical explosion of a single wire in air and
vacuum was studied experimentally. Simultaneous use of optical, UV, and X-ray diagnostics made it possible to distinguish
qualitatively different regions of the discharge channel, such as the current-carrying layers and the region occupied by a
weakly conducting cold plasma. Several series of experiments with 25-μm-diameter 12-mm-long wires made of different materials
were performed. The charging voltage and the current amplitude were varied in the ranges of U
0 = 10–20 kV and I
max ∼ 5–10 kA, respectively. Explosion regimes with a current pause and with and without current interruption, as well as with
wire preheating in air and vacuum, were studied. Shadow and schlieren images of the discharge channel were obtained using
optical probing at the second harmonic of a YAG: Nd+3 laser (λ = 0.532 μm, τ ∼ 10 ns). In the experiments carried out in vacuum, X-ray images of the discharge channel were also
obtained using an X-pinch as a point source of probing radiation and UV images were recorded using a four-frame MCP camera. 相似文献
8.
UV irradiation has multiple effects on mammalian cells, including modification of ion channel function. The present study
was undertaken to investigate the response of membrane currents in guinea-pig ventricular myocytes to the type A (355, 380
nm) irradiation commonly used in Ca2+ imaging studies. Myocytes configured for whole-cell voltage clamp were generally held at −80 mV, dialyzed with K+-, Na+-free pipette solution, and bathed with K+-free Tyrode’s solution at 22°C. During experiments that lasted for ≈ 35 min, UVA irradiation caused a progressive increase
in slowly-inactivating inward current elicited by 200-ms depolarizations from −80 to −40 mV, but had little effect on background
current or on L-type Ca2+ current. Trials with depolarized holding potential, Ca2+ channel blockers, and tetrodotoxin (TTX) established that the current induced by irradiation was late (slowly-inactivating)
Na+ current (INa). The amplitude of the late inward current sensitive to 100 μM TTX was increased by 3.5-fold after 20–30 min of irradiation. UVA modulation of late INa may (i) interfere with imaging studies, and (ii) provide a paradigm for investigation of intracellular factors likely to
influence slow inactivation of cardiac INa. 相似文献
9.
Aspects of body size and gonadal histology in the Antarctic toothfish, Dissostichus mawsoni, from McMurdo Sound, Antarctica 总被引:4,自引:4,他引:0
Twenty-eight specimens of the large notothenioid Dissostichus mawsoni were dissected after capture on a set line near the southern limit of its range in McMurdo Sound, Antarctica. Total length
(L
T) averaged 127.3 cm (range 90–162 cm) and weight (W ) was 26.7 kg (range 10.4–60.3 kg). The length-weight relationship was W=3.44×10−5
L
T
2.85 (n=28, r
2=0.96). Subcutaneous lipid thickness averaged 2.6 mm and showed no difference due to sex, but a significant weak relationship
to W and L
T. Hepatosomatic index (I
H) was 1.6% for females and 1.7% for males; gonadosomatic index (I
G) was 0.9% for females and 0.2% for males. Although specimens were large and sexually mature, the histology indicated that
the gonads of this November sample were in a resting stage. Testes lacked spermatids and spermatozoa. Oocytes were in the
previtellogenic stage (91.2%) or in the first stage of vitellogenesis (8.8%). A few atretic oocytes and empty follicles indicated
that some females in this sample had spawned previously. A summary of the life-cycle is also presented.
Accepted: 27 September 1999 相似文献
10.
Icilin is recognized as a chemical agonist of nociceptors and can activate TRPM8 channels. However, whether this agent has
any effects on immune cells remains unknown. In this study, the effects of icilin on ion currents were investigated in RAW
264.7 murine macrophage-like cells. Icilin (1–100 μM) increased the amplitude of nonselective (NS) cation current (I
NS) in a concentration-dependent manner with an EC50 value of 8.6 μM. LaCl3 (100 μM) or capsazepine (30 μM) reversed icilin-induced I
NS; however, neither apamin (200 nM) nor iberiotoxin (200 nM) had any effects on it. In cell-attached configuration, when the
electrode was filled with icilin (30 μM), a unique population of NS cation channels were activated with single-channel conductance
of 158 pS. With the use of a long-lasting ramp pulse protocol, increasing icilin concentration produced a left shift in the
activation curve of NS channels, with no change in the slope factor of the curve. The probability of channel opening enhanced
by icilin was increased by either elevated extracellular Ca2+ or application of ionomycin (10 μM), while it was reduced by BAPTA-AM (10 μM). Icilin-stimulated activity is associated with
an increase in mean open time and a reduction in mean closed time. Under current-clamp conditions, icilin caused membrane
depolarization. Therefore, icilin interacts with the TRPM8-like channel to increase I
NS and depolarizes the membrane in these cells. 相似文献
11.
S. Bröer A. Schuster C.A. Wagner A. Bröer I. Forster J. Biber H. Murer A. Werner F. Lang A.E. Busch 《The Journal of membrane biology》1998,164(1):71-77
Expression of the protein NaPi-1 in Xenopus oocytes has previously been shown to induce an outwardly rectifying Cl− conductance (GCl), organic anion transport and Na+-dependent P
i
-uptake. In the present study we investigated the relation between the NaPi-1 induced GCl and P
i
-induced currents and transport. NaPi-1 expression induced P
i
-transport, which was not different at 1–20 ng/oocyte NaPi-1 cRNA injection and was already maximal at 1–2 days after cRNA
injection. In contrast, GCl was augmented at increased amounts of cRNA injection (1–20 ng/oocyte) and over a five day expression period. Subsequently
all experiments were performed on oocytes injected with 20 ng/oocytes cRNA. P
i
-induced currents (Ip) could be observed in NaPi-1 expressing oocytes at high concentrations of P
i
(≥ 1 mm P
i
). The amplitudes of Ip correlated well with GCl. Ip was blocked by the Cl− channel blocker NPPB, partially Na+-dependent and completely abolished in Cl− free solution. In contrast, P
i
-transport in NaPi-1 expressing oocytes was not NPPB sensitive, stronger depending on extracellular Na+ and weakly affected by Cl− substitution. Endogenous P
i
-uptake in water-injected oocytes amounted in all experiments to 30–50% of the Na+-dependent P
i
-transport observed in NaPi-1 expressing oocytes. The properties of the endogenous P
i
-uptake system (K
m
for P
i
> 1 mm; partial Na+- and Cl−-dependence; lack of NPPB block) were similar to the NaPi-1 induced P
i
-uptake, but no Ip could be recorded at P
i
-concentrations ≤3 mm. In summary, the present data suggest that Ip does not reflect charge transfer related to P
i
-uptake, but a P
i
-mediated modulation of GCl.
Received: 22 October 1997/Revised: 24 March 1998 相似文献
12.
Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of
other types of channels, a process called cross-talk. The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system, respectively. Currently, cross-talk
between the NMDA receptor and the GABAA receptor, particularly in the central auditory system, is not well understood. In the present study, we investigated functional
interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus, which is an important
nucleus in the central auditory system. We found that the currents induced by aspartate at 100 μmol L−1 were suppressed by the pre-perfusion of GABA at 100 μmol L−1, indicating cross-inhibition of NMDA receptors by activation of GABAA receptors. Moreover, we found that the currents induced by GABA at 100 μmol L−1 (I
GABA) were not suppressed by the pre-perfusion of 100 μmol L−1 aspartate, but those induced by GABA at 3 μmol L−1 were suppressed, indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors. In addition, inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+, however, CdCl2 effectively attenuated the inhibition of I
GABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L−1 BAPTA, a membrane-permeable Ca2+ chelator, suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors, rather than voltage-dependent Ca2+ channels. Finally, KN-62, a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), reduced the inhibition of I
GABA by aspartate, indicating the involvement of CaMKII in this cross-inhibition. Our study demonstrates a functional interaction
between NMDA and GABAA receptors in the inferior colliculus of rats. The presence of cross-talk between these receptors suggests that the mechanisms
underlying information processing in the central auditory system may be more complex than previously believed. 相似文献
13.
Regulation of calcium current through L-type calcium channels (I
Ca,L) of the guinea pigtaenia coli smooth muscle cell (SMC) membrane by cyclic nucleotides and protein kinase C (PKC) was studied using a voltage-clamp technique
with intracellular dialysis or membrane patch perforation with amphotericin B. Non-selective blockers of serine/threonine
kinase, staurosporine and H-7 reduced theI
Ca,L amplitude in a dose-dependent manner. Dose-dependent suppression ofI
Ca,L was also produced by a selective PKC blocker, chelerythrine, and a cAMP-and cGMP-dependent protein kinase (PKA, PKG), blocker
H-8. Forskolin, which increases the intracellular level of cAMP, as well as membrane-permeant cAMP analogs, dibutyryl-cAMP
(db-cAMP) and 8-bromo-cAMP, exerted complex effects onI
Ca,L. The latter increased at their concentrations below 10 μM and decreased at their higher concentrations. 8-Bromo-cGMP reducedI
Ca,L in all cases. Addition of 50 μM GTPγS to the micropipette solution caused a marked and slowly developing increase inI
Ca,L. 8-Bromo-cAMP (1 μM) increasedI
Ca,L by 30%, both in the control and during the action of GTPγS. The blockade of PKC by 10 μM chelerythrine removed the effect
of GTPγS onI
Ca,L. The results suggest that basal activity of L-type calcium channels in SMC of the guinea pigtaenia coli depends on PKC- and PKA-dependent phosphorylation. PKC can increase theI
Ca,L amplitude provided G proteins are activated. cAMP at low concentrations likewise increasesI
Ca,L (probably through activation of PKA). PKG apparently mediatesI
Ca,L drops evoked by cAMP at high concentrations and by cGMP. 相似文献
14.
Transient outward currents were characterized with twin electrode voltage clamp techniques in isolated F76 and D1 neuronal
membranes (soma only) of Helix aspersa subesophageal ganglia. In this study, in addition to the transient outward current (A-current, I
A
) described by Connor and Stevens (1971b), another fast outward current, referred to as I
Adepol
here, is described for the first time. This is similar to the current component characterized in Aplysia (Furukawa, Kandel & Pfaffinger, 1992). The separation of these two current components was based on activation and steady-state
inactivation curves, holding potentials and sensitivity to 4-aminopyridine (4-AP). In contrast to I
A
, I
Adepol
did not require hyperpolarizing conditioning pulses to remove inactivation; it was evoked from a holding potential of −40
mV, at which I
A
is completely inactivated. I
Adepol
shows noticeable activation at around −5 mV, whereas I
A
activates at around −50 mV. The time courses of I
Adepol
activation and inactivation were similar but slower than I
A
. It was found that I
Adepol
was more sensitive than I
A
to 4-AP. 4-AP at a concentration of 1 mm blocked I
Adepol
completely, whereas 5–6 mm 4-AP was needed to block I
A
completely. This current is potentially very important because it may, like other A currents, regulate firing frequency but
notably, it does not require a period of hyperpolarization to be active.
Received: 12 May 2000/Revised: 12 October 2000 相似文献
15.
Oliveira EE Schleicher S Büschges A Schmidt J Kloppenburg P Salgado VL 《Insect biochemistry and molecular biology》2011,41(11):872-880
Imidacloprid, sulfoxaflor and two experimental sulfoximine insecticides caused generally depressive symptoms in stick insects, characterized by stillness and weakness, while also variably inducing postural changes such as persistent ovipositor opening, leg flexion or extension and abdomen bending that could indicate excitation of certain neural circuits. We examined the same compounds on nicotinic acetylcholine receptors in stick insect neurons, which have previously been shown to desensitize in the presence of ACh. Brief U-tube application of 10−4 M solutions of insecticides for 1 s evoked currents that were much smaller than ACh-evoked currents, and depressed subsequent ACh-evoked currents for several minutes, indicating that the compounds are low-efficacy partial agonists that potently desensitize the receptors. Much lower concentrations of insecticides applied in the bath for longer periods did not activate currents, but inhibited ACh-evoked currents via desensitization of the receptors. Previously described fast- and slowly-desensitizing nACh currents, IACh1 and IACh2 respectively, were each found to consist of two components with differing sensitivities to the insecticides. Imidacloprid applied in the bath desensitized high-sensitivity components, IACh1H and IACh2H with IC50s of 0.18 and 0.13 pM, respectively. It desensitized the low-sensitivity slowly desensitizing component, IACh2L, with an IC50 of 2.6 nM, while a component of the fast-desensitizing current, IACh1L, was least sensitive, with an IC50 of 81 nM IACh1L appeared to be insensitive to the three sulfoximines tested, whereas all three sulfoximines potently desensitized IACh1H and both slowly desensitizing components, with IC50s between 2 and 7 nM. We conclude that selective desensitization of certain nAChR subtypes can account for the insecticidal actions of imidacloprid and sulfoximines in stick insects. 相似文献
16.
O. V. Bolotov V. I. Golota B. B. Kadolin V. I. Karas’ V. N. Ostroushko L. M. Zavada A. Yu. Shulika 《Plasma Physics Reports》2010,36(11):1000-1011
Results are presented from experimental studies of cathode-directed streamers in the gap closure regime without a transition
into spark breakdown. Spatiotemporal, electrodynamic, and spectroscopic characteristics of streamer discharges in air at different
pressures were studied. Similarity laws for streamer discharges were formulated. These laws allow one to compare the discharge
current characteristics and streamer propagation dynamics at different pressures. Substantial influence of gas photoionization
on the deviations from the similarity laws was revealed. The existence of a pressure range in which the discharges develop
in a similar way was demonstrated experimentally. In particular, for fixed values of the product pd and discharge voltage U, the average streamer velocity is also fixed. It is found that, although the similarity laws are violated in the interstreamer
pause of the discharge, the average discharge current and the product of the pressure and the streamer repetition period remain
the same at different pressures. The radiation spectra of the second positive system of nitrogen (the C3Π
u
-B3Π
g
transitions) in a wavelength range of 300–400 nm at air pressures of 1–3 atm were recorded. It is shown that, in the entire
pressure range under study, the profiles of the observed radiation bands practically remain unchanged and the relative intensities
of the spectral lines corresponding to the 3Π
u
-B3Π
g
transitions are preserved. 相似文献
17.
The THP-1 human monocytic leukemia cell line is a useful model of macrophage differentiation. Patch clamp methods were used
to identify five types of ion channels in undifferentiated THP-1 monocytes. (i) Delayed rectifier K+ current, I
DR, was activated by depolarization to potentials positive to −50 mV, inactivated with a time constant of several hundred msec,
and recovered from inactivation with a time constant ∼21 sec. I
DR was inhibited by 4-aminopyridine (4-AP), tetraethylammonium (TEA+), and potently by charybdotoxin (ChTX). (ii) Ca-activated K+ current (I
SK) dominated whole-cell currents in cells studied with 3–10 μm [Ca2+]
i
. I
SK was at most weakly voltage-dependent, with reduced conductance at large positive potentials, and was inhibited by ChTX and
weakly by TEA+, Cs+, and Ba2+, but not 4-AP or apamin. Block by Cs+ and Ba2+ was enhanced by hyperpolarization. (iii) Nonselective cation current, I
cat, appeared at voltages above +20 mV. Little time-dependence was observed, and a panel of channel blockers was without effect.
(iv) Chloride current, I
Cl, was present early in experiments, but disappeared with time. (v) Voltage-activated H+ selective current is described in detail in a companion paper (DeCoursey & Cherny, 1996. J. Membrane Biol.
152:2). The ion channels in THP-1 cells are compared with channels described in other macrophage-related cells. Profound changes
in ion channel expression that occur during differentiation of THP-1 cells are described in a companion paper (DeCoursey et
al., 1996. J. Membrane Biol.
152:2).
Received: 19 September 1995/Revised: 14 March 1996 相似文献
18.
Excitatory effect of ATP on rat area postrema neurons 总被引:1,自引:0,他引:1
ATP-induced inward currents and increases in the cytosolic Ca2+ concentration ([Ca]in) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microfluorometry, respectively. The ATP-induced current (I
ATP) and [Ca]in increases were mimicked by 2-methylthio-ATP and ATP-γS, and were inhibited by P2X receptor (P2XR) antagonists. The current–voltage relationship of the I
ATP exhibited a strong inward rectification, and the amplitude of the I
ATP was concentration-dependent. The I
ATP was markedly reduced in the absence of external Na+, and the addition of Ca2+ to Na+-free saline increased the I
ATP. ATP did not increase [Ca]in in the absence of external Ca2+, and Ca2+ channel antagonists partially inhibited the ATP-induced [Ca]in increase, indicating that ATP increases [Ca]in by Ca2+ influx through both P2XR channels and voltage-dependent Ca2+ channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current flow through either channel. Current occlusion was observed at V
hs between −70 and −10 mV when the I
ATP and ACh-induced current (I
ACh) were inward, but no occlusion was observed when these currents were outward at a V
h of +40 mV. The I
ATP was not inhibited by co-application of ACh when the I
ACh was markedly decreased either by removal of permeant cations, by setting V
h close to the equilibrium potential of I
ACh, or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current flow of cations through the activated P2XR- and nAChR-channels. 相似文献
19.
Rat forebrain- and heart-derived mRNA were used to express Ca2+ channels inXenopus oocytes to study their cAMP-dependent regulation. Forebrain and heart mRNA-directed Ca2+ channel currents (I
Ba, 40 mM Ba2+ were used as a charge carrier) showed similar voltage dependence and macroscopic kinetics but different pharmacology, which
allowed us to attribute them to N- and L-type, respectively. Brain mRNA-directedI
Ba was insensitive to the dihydropyridine (DHP) antagonist nitrendipine and the agonist Bay K 8644, but could be inhibited by
70% by 1 μM of ω-conotoxin GVIA, whileI
Ba directed by cardiac mRNA was extremely sensitive to DHP. Neither forebrain, nor heart mRNA-directedI
Ba could be augmented by the external applications of the β-agonist isoproterenol (ISO, 10 μM), the adenylate cyclase (AC) activator
forskolin (FSK, 10 μM), the phosphodiesterase inhibitor IBMX (200 μM), or their mixtures. “Cardiac”I
Ba was also unresponsive to the external applications of a membrane-permeable cAMP analog 8-(4-chlorophenylthio)-cAMP (500 μM),
as well as to the direct intracellular infusion of cAMP (300 μM). Blockade of cAMP-dependent phosphorylation pathway by intracellular
perfusion of the oocytes with 200 μM Rp-cAMP plus 200 μM of a synthetic protein kinase A (PKA) inhibitor peptide also exerted
no effect on the basal level ofI
Ba, suggesting that the expressed Ca2+ channels are not fully phosphorylated in the resting state. Measurements of the concentration of cAMP in the control and
heart mRNA-injected oocytes, using an enzyme-immunoassay system, showed that they display a similar basal cAMP concentration
(2.0–2.5 μM); however, application of ISO + FSK increased the cAMP concentration 2- to 3-fold in mRNA-injected oocytes, but
not in control oocytes. Thus, our data demonstrate that injection of rat cardiac mRNA intoXenopus oocytes results in the expression of receptor-stimulated AC and L-type Ca2+ channels, which do not respond to cAMP or PKA inhibitors. Unresponsiveness to cAMP-dependent regulation is not channel type-specific,
since N-type Ca2+ channels expressed by means of forebrain mRNA are also insensitive to such regulation. Unresponsiveness of the channels to
cAMP-mediated regulation is most probably due to lack/inaccessibility of PKA-dependent phosphorylation site(s), or loss of
functional significance of phosphorylation. 相似文献
20.
ON and OFF retinal ganglion cells (RGCs) display differences in their intrinsic electrophysiology: OFF cells maintain spontaneous
activity in the absence of any input, exhibit subthreshold membrane potential oscillations, rebound excitation and burst firing;
ON cells require excitatory input to drive their activity and display none of the aforementioned phenomena. The goal of this
study was to identify and characterize ionic currents that explain these intrinsic electrophysiological differences between
ON and OFF RGCs. A mathematical model of the electrophysiological properties of ON and OFF RGCs was constructed and validated
using published patch-clamp data from isolated intact mouse retina. The model incorporates three ionic currents hypothesized
to play a role in generating behaviors that are different between ON and OFF RGCs. These currents are persistent Na + , I
NaP, hyperpolarization-activated, I
h, and low voltage activated Ca2 + , I
T, currents. Using computer simulations of Hodgkin-Huxley type neuron with a single compartment model we found two distinct
sets of I
NaP, I
h, I
T conductances that correspond to ON and OFF RGCs populations. Simulations indicated that special properties of I
T explain the differences in intrinsic electrophysiology between ON and OFF RGCs examined here. The modelling shows that the
maximum conductance of I
T is higher in OFF than in ON cells, in agreement with recent experimental data. 相似文献