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1.
We studied the effect of 4-aminopyridine (4-AP) on the channels responsible for transient rapidly inactivating potassium A-type
current ( I
A
) in the somatic membrane of cultured rat hippocampal neurons. External application of 4-AP in different concentrations (from
100 μM to 5mM) was made to the locus of the neuron under study using a fast local superfusion technique. The I
A
blockade was dose-dependent and voltage-independent. Interaction of the blocker with the I
A
-conducting channels at a test potential of +40 mV could be approximated by Hill isotherm with the cooperativity coefficient
of 2 and EC 50 equal to 2.1 mM. The action of 4-AP accelerated temporal inactivation of I
A
. The intensity of I
A
blockade became higher as the frequency of test membrane potential shifts increased. 相似文献
2.
Elevation of the external potassium concentration induced a two-phase inward current in freshly isolated pyramidal hippocampal
neurons. This current was voltage-dependent and demonstrated strong inward rectification. The current consisted of a leakage
current and a time-dependent current (τ=40–50 msec at 21°C); the latter was designated as I
ΔK. As was shown earlier, K + is a major charge carrier in the development of slow potassium-activated current. The pharmacological properties of I
ΔK were studied using a patch-clamp technique. I
ΔK was completely blocked by external 10 mM TEA or 5 mM Ba 2+ (IC 50=480±90 mM) and exhibited low sensitivity to extracellular Cs + (2 mM). This current was not affected by 1 mM 4-aminopyridine and was insensitive to a muscarinic agonist, carbachol (50
μM), and to 1 mM extracellular Cd 2+. Elevation of external Ca 2+ from 2.5 mM to 10 mM did not change I
ΔK. Our data indicate that the pharmacological properties of I
ΔK differ from those of other voltage-gated potassium currents, but more specific blockers must be used to make this evidence
conclusive. 相似文献
3.
General anesthetics thiopental and pentobarbital possess very similar chemical structures whereas their clinical potency is
quite different. The underlying molecular mechanism is not fully understood. This study was designed to assess the differential
effects of thiopental and pentobarbital on GABA A receptors of mechanically dissociated rat spinal dorsal horn neurons by using whole-cell patch-clamp technique. Pentobarbital,
at a concentration of 30 μM, which markedly enhanced sub-saturated GABA-induced current ( I
GABA), had no effect on thiopental-induced maximal current. Similarly, the pentobarbital-induced maximal current was also not
affected by 30 μM thiopental. Moreover, a linear summation of thiopental-induced maximal current and pentobarbital-induced
sub-maximal current was observed. In addition, pentobarbital failed to further enhance I
GABA in the presence of thiopental at a concentration with maximal modulatory effects on I
GABA, and vice versa. Our results thus suggest that thiopental and pentobarbital might exert the GABA mimetic effects independently,
but share a common mechanism to produce the GABA modulatory effects.
Special issue article in honor of Dr. Ji-Sheng Han. 相似文献
4.
The effects of sodium metabisulfite (SMB), a general food preservative, on potassium currents in rat dorsal root ganglion
(DRG) neurons were investigated using the whole-cell patch-clamp technique. SMB increased the amplitudes of both transient
outward potassium currents and delayed rectifier potassium current in concentration- and voltage-dependent manner. The transient
outward potassium currents (TOCs) include a fast inactivating (A-current or I
A) current and a slow inactivating (D-current or I
D) current. SMB majorly increased I A, and I D was little affected. SMB did not affect the activation process of transient outward currents (TOCs), but the inactivation
curve of TOCs was shifted to more positive potentials. The inactivation time constants of TOCs were also increased by SMB.
For delayed rectifier potassium current ( I
K), SMB shifted the activation curve to hyperpolarizing direction. SMB differently affected TOCs and I
K, its effects major on A-type K + channels, which play a role in adjusting pain sensitivity in response to peripheral redox conditions. SMB did not increase
TOCs and I
K when adding DTT in pipette solution. These results suggested that SMB might oxidize potassium channels, which relate to adjusting
pain sensitivity in pain-sensing DRG neurons. 相似文献
5.
Voltage-gated potassium (KV) currents, subdivided into rapidly inactivating A-type currents (I
A) and slowly inactivating delayed rectifier currents (I
K), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on KV currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I
A and I
K in concentration-dependent manner. The IC50 values for block of I
A and I
K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I
A and I
K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I
A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I
A and I
K channels, and has no effect on the resting state and inactivated state of the I
A channel. Blockade on K+ channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain. 相似文献
6.
运用全细胞膜片钳技术研究二氧化硫衍生物对大鼠背根神经元瞬间外向钾电流(IA和ID)和延迟整流钾电流(IK)的影响。结果发现二氧化硫衍生物剂量依赖性地增大钾通道的电导,电压依赖性地增大钾电流的幅度,且这种增大作用部分可逆。二氧化硫非常显著地使延迟整流钾电流的激活过程向超极化方向移动,使瞬间外向钾电流的失活过程向去极化方向移动。10μmol/L二氧化硫衍生物作用前后,延迟整流钾电流的半数激活电压分别是(20.3±2.1)mV和(15.0±1.5)mV;IA和ID的半数失活电压分别朝去极化方向移动了6mV和7.4mV。这些结果表明二氧化硫改变了钾通道的特性,改变了神经元的兴奋性。 相似文献
7.
Regulation of calcium current through L-type calcium channels ( I
Ca,L) of the guinea pig taenia 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 the I
Ca,L amplitude in a dose-dependent manner. Dose-dependent suppression of I
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 on I
Ca,L. The latter increased at their concentrations below 10 μM and decreased at their higher concentrations. 8-Bromo-cGMP reduced I
Ca,L in all cases. Addition of 50 μM GTPγS to the micropipette solution caused a marked and slowly developing increase in I
Ca,L. 8-Bromo-cAMP (1 μM) increased I
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 on I
Ca,L. The results suggest that basal activity of L-type calcium channels in SMC of the guinea pig taenia coli depends on PKC- and PKA-dependent phosphorylation. PKC can increase the I
Ca,L amplitude provided G proteins are activated. cAMP at low concentrations likewise increases I
Ca,L (probably through activation of PKA). PKG apparently mediates I
Ca,L drops evoked by cAMP at high concentrations and by cGMP. 相似文献
8.
It is widely believed, following the work of Connor and Stevens (1971, J. Physiol. Lond.
214, 31–53) that the ability to fire action potentials over a wide frequency range, especially down to very low rates, is due
to the transient, potassium A-current ( I
A). Using a reduction of the classical Hodgkin-Huxley model, we study the effects of I
A on steady firing rate, especially in the near-threshold regime for the onset of firing. A minimum firing rate of zero corresponds
to a homoclinic bifurcation of periodic solutions at a critical level of stimulating current. It requires that the membrane's
steady-state current-voltage relation be N-shaped rather than monotonic. For experimentally based generic I
A parameters, the model does not fire at arbitrarily low rates, although it can for the more atypical I
A parameters given by Connor and Stevens for the crab axon. When the I
A inactivation rate is slow, we find that the transient potassium current can mediate more complex firing patterns, such as
periodic bursting in some parameter regimes. The number of spikes per burst increases as g
A decreases and as inactivation rate decreases. We also study how I
A affects properties of transient voltage responses, such as threshold and firing latency for anodal break excitation. We provide
mathematical explanations for several of these dynamic behaviors using bifurcation theory and averaging methods. 相似文献
9.
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 EC 50 value of 8.6 μM. LaCl 3 (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 Ca 2+ 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
10.
Summary The effects of the calcium antagonist D-600 (methoxyverapamil) on the excitatory inward sodium current, I
Na, of internally perfused squid giant axons were studied under voltageclamp conditions. We observed little or no effect of the drug when it was added to the external solution at concentrations of 10–200 M. Furthermore, it did not produce a frequency, or use-dependent block of I
Na when repetitive voltage-clamp pulses were used at rates of 2–5Hz. However, it did produce use-dependent blockade of I
Na when it was placed internally at a concentration of 200 M. These results in conjunction with other studies suggest that D-600 is a selective blocker of calcium channels in squid axons when the drug is placed in the external solution. Its effects, when placed in the internal solution, are similar to those of permanently charged local anesthetic derivatives, which also produce use-dependent block of I
Na. 相似文献
11.
Rat forebrain- and heart-derived mRNA were used to express Ca 2+ channels in Xenopus oocytes to study their cAMP-dependent regulation. Forebrain and heart mRNA-directed Ca 2+ channel currents ( I
Ba, 40 mM Ba 2+ 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-directed I
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, while I
Ba directed by cardiac mRNA was extremely sensitive to DHP. Neither forebrain, nor heart mRNA-directed I
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 of I
Ba, suggesting that the expressed Ca 2+ 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 into Xenopus oocytes results in the expression of receptor-stimulated AC and L-type Ca 2+ channels, which do not respond to cAMP or PKA inhibitors. Unresponsiveness to cAMP-dependent regulation is not channel type-specific,
since N-type Ca 2+ 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
12.
Heart cells from the clam Ruditapes decussatus were routinely cultured with a high level of reproducibility in sea water based medium. Three cell types attached to the
plastic after 2 days and could be maintained in vitro for at least 1 month: epithelial-like cells, round cells and fibroblastic
cells. Fibroblastic cells were identified as functional cardiomyocytes due to their spontaneous beating, their ultrastructural
characteristics and their reactivity with antibodies against sarcomeric α-actinin, sarcomeric tropomyosin, myosin and troponin
T-C. Patch clamp measurements allowed the identification of ionic currents characteristic of cardiomyocytes: a delayed potassium
current ( I
K slow) strongly suppressed (95%) by tetraethylammonium (1 mM), a fast inactivating potassium current ( I
K fast) inhibited (50%) by 4 amino-pyridine at 1 mM and, at a lower level (34%) by TEA, a calcium dependent potassium current ( I
KCa) activated by strong depolarization. Three inward voltage activated currents were also characterized in some cardiomyocytes:
L-type calcium current ( I
Ca) inhibited by verapamil at 5 × 10 −4 M, T-type Ca 2+ current, rapidly activated and inactivated, and sodium current ( I
Na) observed in only a few cells after strong hyperpolarization. These two currents did not seem to be physiologically essential
in the initiation of the beatings of cardiomyocytes. Potassium currents were partially inhibited by tributyltin (TBT) (1 μM)
but not by okadaic acid (two marine pollutants). DNA synthesis was also demonstrated in few cultured cells using BrdU (bromo-2′-deoxyuridine).
Observed effects of okadaic acid and TBT demonstrated that cultured heart cells from clam Ruditapes decussatus can be used as an experimental model in marine toxicology. 相似文献
13.
Dopamine (DA) released from the hypothalamus tonically inhibits pituitary lactotrophs. DA (at micromolar concentration) opens
potassium channels, hyperpolarizing the lactotrophs and thus preventing the calcium influx that triggers prolactin hormone
release. Surprisingly, at concentrations ∼1000 lower, DA can stimulate prolactin secretion. Here, we investigated whether
an increase in a K + current could mediate this stimulatory effect. We considered the fast K + currents flowing through large-conductance BK channels and through A-type channels. We developed a minimal lactotroph model
to investigate the effects of these two currents. Both I
BK and I
A could transform the electrical pattern of activity from spiking to bursting, but through distinct mechanisms. I
BK always increased the intracellular Ca 2+ concentration, while I
A could either increase or decrease it. Thus, the stimulatory effects of DA could be mediated by a fast K + conductance which converts tonically spiking cells to bursters. In addition, the study illustrates that a heterogeneous distribution
of fast K + conductances could cause heterogeneous lactotroph firing patterns.
Action Editor: Christiane Linster 相似文献
14.
The modulation of I
A
K + current by ten trivalent lanthanide (Ln 3+) cations spanning the series with ionic radii ranging from 0.99 ? to 1.14 ? was characterized by the whole-cell patch clamp
technique in bovine adrenal zona fasciculata (AZF) cells. Each of the ten Ln 3+s reduced I
A
amplitude measured at +20 mV in a concentration-dependent manner. Smaller Ln 3+s were the most potent and half-maximally effective concentrations (EC 50s) varied inversely with ionic radius for the larger elements. Estimation of EC 50s yielded the following potency sequence: Lu 3+ (EC 50= 3.0 μ m) ≈ Yb 3+ (EC 50= 2.7 μ m) > Er 3+ (EC 50= 3.7 μ m) ≥ Dy 3+ (EC 50= 4.7 μ m) > Gd 3+ (EC 50= 6.7 μ m) ≈ Sm 3+ (EC 50= 6.9 μ m) > Nd 3+ (EC 50= 11.2 μ m) > Pr 3+ (EC 50= 22.3 μ m) > Ce 3+ (EC 50= 28.0 μ m) > La 3+ (EC 50= 33.7 μ m).
Ln 3+s altered selected voltage-dependent gating and kinetic parameters of I
A
with a potency and order of effectiveness that paralleled the reduction of I
A
amplitude. Ln 3+s markedly slowed activation kinetics and shifted the voltage-dependence of I
A
gating such that activation and steady-state inactivation occurred at more depolarized potentials. In contrast, Ln 3+s did not measurably alter inactivation or deactivation kinetics and only slightly slowed kinetics of inactivated channels
returning to the closed state. Replacement of external Ca 2+ with Mg 2+ had no effect on the concentration-dependent inhibition of I
A
by Ln 3+s. In contrast to their action on I
A
K + current, Ln 3+s inhibited T-type Ca 2+ currents in AZF cells without slowing activation kinetics.
These results indicate that Ln 3+ modulate I
A
K + channels through binding to a site on I
A
channels located within the electric field but which is not specific for Ca 2+. They are consistent with a model where Ln 3+ binding to negative charges on the gating apparatus alters the voltage-dependence and kinetics of channel opening. Ln 3+s modulate transient K + and Ca 2+ currents by two fundamentally different mechanisms.
Received: 21 January 1997/Revised: 3 April 1998 相似文献
15.
A low-threshold outward current was studied in the neurons of Helix pomatia at –70 to –30 mV using a two-electrode voltage clamp technique. In addition to the well-known A current ( I
A), a slower outward current called I
As (slow) was revealed. Activation and inactivation times of I
As at –40 mV ranged from 90 to 120 msec and from 3 to 5 sec, respectively. The current recovered within 2 to 5 sec after inactivation at –120 mV. Analysis of changes in the reversal potential of I
As caused by an increase in external potassium concentration suggests a potassium origin for I
As. The curves of I
As stationary activation and inactivation fit the Boltzmann equation. Deriving from an activation curve, the activation potential for a half-maximum current,, is –40 mV, and the slope factor, k, is –9.8 mV, while those values for the inactivation curve are –84 mV (a half-maximum inactivation) and 7.5 mV. I
As is blocked by 4-aminopyridine (1–30 µM), tetraethylammonium (1 mM), and Ba 2+ (1 mM), but is resistant to Cs + (1 mM). Peak I
As is not affected either by substitution of external Ca 2+ for Mg 2+ or by application of Cd 2+ (0.5–1.0 mM). The results suggest that activation of I
As does not require Ca 2+ entry into the cell.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 427–432, November–December, 1993. 相似文献
16.
Earlier, we have shown a strong inhibitory effect of donepezil on K +-current of molluscan neurons (Solntseva et al., Comp Biochem Physiol 144, 319–326, 2007). In the present work, a possible
interaction of donepezil with the external mouth of the channel was examined using, as a tool, tetraethylammonium (TEA), a
classical antagonist of potassium channels. Experiments were conducted in isolated neurons of snail Helix aspersa using the
two-microelectrode voltage-clamp technique. A high-threshold slow-inactivating K +-current involving Ca 2+-dependent ( I
C) and Ca 2+-independent ( I
K) components was recorded. The I
C was estimated at 30 mV, and I
K at 100 mV. The IC 50 values for blocking effect of donepezil on I
C varied from 5.0 to 8.9 μM in different cells. Corresponding values for I
K varied from 4.9 to 9.9 μM. The IC 50 values for blocking effect of TEA on I
C lied in the range of 200 to 910 μM, and on I
K lied in the range of 100 to 990 μM. The comparison of the effects of donepezil and TEA on the same cells revealed significant
correlation between IC 50 values of these effects. The value of Spearman coefficient of correlation ( r) was 0.77 for I
C ( P < 0.05), and 0.82 for I
K ( P < 0.05). In the presence of TEA, the effect of donepezil, both on I
C and I
K, appears significantly weaker than in control solution. Dose–response curves of donepezil effect both on I
C and I
K were shifted right along horizontal axis when donepezil was applied in combination with TEA. Results suggest that TEA interferes
with donepezil and precludes the occupation by donepezil of its own site. We suppose that the site for donepezil is situated
near the TEA site with possible overlap. 相似文献
17.
Cell intermediary metabolism and energy production succeeds by means of mitochondria, whose activity is in relation to transmembrane
potential and/or free radical production. Adenosine triphosphate (ATP)-dependent potassium channels (K ATP) in several cell types have shown to couple cell metabolism to membrane potential and ATP production. In this study, we explore
whether oxygen consumption in isolated skeletal-muscle mitochondria differs in the presence of distinct respiration substrates
and whether these changes are affected by K ATP-channel inhibitors such as glibenclamide, 5-Hydroxydecanoate (5-HD), and K ATP channel activators (pinacidil and diazoxide). Results demonstrate a concentration-dependent diminution of respiration rate
by glibenclamide (0.5–20 μM), pinacidil (1–50 μM), and diazoxide (50–200 μM), but no significant differences were found when
the selective mitochondrial K ATP-channel inhibitor (5-HD, 10–500 μM) was used. These results suggest that these K ATP-channel agonists and antagonists exert an effect on mitochondrial respiration and that they could be acting on mito-K ATP or other respiratory-chain components. 相似文献
18.
Three fenamates—niflumic, flufenamic and mefenamic acids—were tested for effects on substrate-induced currents of glutamate
and glycine transporters (EAAT1, EAAT2, GLYT1b and GLYT2a) expressed in Xenopus laevis oocytes. All fenamates inhibited EAAT1 currents; 100 μM flufenamic acid produced the most inhibition, decreasing the I
max by 53 ± 4% ( P < 0.001). EAAT2 currents were less sensitive, but 100 μM flufenamic acid inhibited the I
max by 34 ± 5% ( P = 0.006). All fenamates inhibited GLYT1b currents; 100 μM flufenamic acid produced the most inhibition, decreasing the I
max by 61 ± 1% ( P < 0.001). At 100 μM, effects on the GLYT2a I
max were mixed: 13 ± 2% inhibition by flufenamic acid ( P = 0.002), 30 ± 6% enhancement by niflumic acid ( P = 0.002), and no effect by mefenamic acid. Minor effects on substrate affinity suggested non-competitive mechanisms. These
data could contribute to the development of selective transport modulators. 相似文献
19.
The responses of freshly isolated hippocampal pyramidal neurons to rapid, elevations of the external potassium concentration
([K +]
out
) were investigated using the whole-cell variation of a patch-clamp technique. An elevation of [K +]
out
induced a two-phase inward current at the membrane potentials more negative than the reversal potential for K ions. This
current consisted of a leakage, current and a time-dependent current (τ=40–50 msec at 21°C), the latter designated below as I
ΔK. It displayed first-order activation kinetics that showed neither voltage, nor concentration dependence. The amplitude of
this current was determined by the external K + concentration and increased with hyperpolarization. Voltage dependence of I
ΔK measured within the range from −20 to −120 mV was similar to that for inward rectifier. Activation of I
ΔK was utterly dependent on Na +; substitution of extracellular Na + with choline chloride almost completely depressed I
ΔK. I
ΔK was absent in the cells freshly dissociated from the nodosal and dorsal root ganglia. This suggests that this earlier unrecognized
current is instrumental in preserving densely packed hippocampal pyramidal neurons from sudden increases in [K +]
out
and following spontaneous over-excitation. It prevents the neurons from responding to K +-induced depolarizations by slowing down potassium influx. 相似文献
20.
The incidence rates of long QT syndrome (LQTS) and drug-induced torsades de pointes (TDP) are higher in women than men. Although
gonadal steroids are assumed to play an important role in the gender-based differences in cardiac electrophysiological properties,
the underlying mechanisms of the gender-based differences are not fully understood. In particular I
Kr, which comprises the repolarization phase of the action potential, has not been well understood in its modulation by sex
hormones. To assess this, we examined the effects of the female sex hormone β-estradiol on the human ether-a-go-go-related gene ( hERG)-encoded potassium current stably expressed in human embryonic kidney-293 (HEK) cells. We demonstrated that hERG currents
were inhibited by β-estradiol maximally to 62% of control with an IC 50 of 1.3 μM and a Hill coefficient of 0.87, which might account for the sex-related differences in LQTS. We also examined whether
estrogen modulated drug-induced blocking effects on hERG currents or not. With simultaneous application of 10 μM erythromycin,
which is known to block hERG currents but not in low doses, the blocking effects of β-estradiol on hERG currents were enhanced.
Namely, hERG currents were inhibited maximally to 45.8% of control with an IC 50 of 59 nM ( P < 0.02) by β-estradiol with 10 μM erythromycin. We conclude here that a significant block of hERG currents by β-estradiol
may account for the sex-related differences in LQTS and the synergic effects of β-estradiol and erythromycin indicate a higher
risk of drug-induced TDP in women than men. 相似文献
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