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K Muraki

Publications and source records attributed to K Muraki.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of K+ channel modulators on the relationship between action potential duration and Ca2+ transients in single ventricular myocytes of the guinea pig.

Effects of K+ channel modulators, cromakalim and E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4-methylsulfonylaminobenzoyl) piperidine], on the relationship between the action potential duration (APD) and Ca2+ transients were examined in single myocytes isolated from guinea pig cardiac left ventricle. Application of cromakalim decreased APD at 90% repolarization (APD90) and Ca2+ transient elicited at 0.5 Hz (IC50s=0.6 and 3 microM, respectively). Application of 0.3 microM E4031 increased these parameters by 110% and 45%, respectively. Under voltage-clamp, the relation between the duration of depolarization to 0 mV and Ca2+ transients could be described by the sum of two exponential components; the time constants were approximately 5 and 280 msec, respectively. The first component was abolished by 10 microM ryanodine, suggesting the involvement of Ca2+-induced Ca2+ release (CICR). Neither cromakalim nor E4031 directly affected Ca2+ current and Ca2+ transients under voltage clamp. When APD was changed by K+ channel modulators, the relation between APD90 and Ca2+-transients was almost similar to that obtained by changing the depolarization duration under voltage-clamp. CICR was changed significantly only when APD90 was markedly shortened by cromakalim. The extensively prolonged AP and Ca2+ transient in the presence of E4031 were reduced by an addition of cromakalim. It is concluded that these two K+ channel modulators can significantly alter the AP-induced Ca2+ transient mainly by changing APD, which regulates both Ca2+ influx and extrusion.

Action Potentials↗
PubMed1999

Activation of Ca(2+)-dependent K(+) current by nordihydroguaiaretic acid in porcine coronary arterial smooth muscle cells.

The effects of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor and an antioxidant, on membrane currents were examined in single smooth muscle cells isolated from porcine coronary artery. Spontaneous transient outward currents (STOCs) recorded at -30 mV were markedly enhanced by NDGA (>/=10 microM). Pretreatment with caffeine and ryanodine abolished STOCs and reduced NDGA-induced increase in outward current at -30 mV by approximately 60%. NDGA showed dual action on an outward current elicited by step depolarization from -60 to 0 mV: inhibition and enhancement at concentrations of 3 and >/=10 microM, respectively. In the presence of Cd(2+), the inhibition of outward current by NDGA disappeared and the enhancement remained. NDGA inhibited both the voltage-dependent Ca(2+) channel current (IC(50) = 2.5 microM) and the delayed rectifier K(+) current (IC(50) = 9.8 microM). The NDGA-induced enhancement of STOCs and outward currents on depolarization was abolished by 100 nM iberiotoxin but was not affected by glibenclamide or apamin. Under current clamp mode, 30 microM NDGA significantly hyperpolarized myocytes. The application of lipoxygenase inhibitors (caffeic acid and esculetin), a cyclooxygenase inhibitor (indomethacin), antioxidants (ascorbic acid and erythorbic acid), and structural-related compounds of NDGA (catechol and dopamine) did not enhance K(+) currents. These results indicate that the opening of the large conductance Ca(2+)-dependent K(+) channel by NDGA, which is independent of its lipoxygenase inhibition or antioxidant effect, results in membrane hyperpolarization.

Animals↗
PubMed1998

Effects of UTP on membrane current and potential in rat aortic myocytes.

The electrophysiological effects of UTP on freshly isolated rat aortic myocytes were examined using the perforated patch clamp technique. Application of alpha,beta-methylene ATP (alphabeta-meATP) and UTP, putative P2X and P2Y2 or P2Y4 purinoceptor agonists, induced transient and oscillatory inward currents, respectively. Experiments with Cl- channel blockers and different external Cl- concentrations demonstrated that the oscillatory current elicited by UTP is attributable to activation of Cl- channels. The transient component elicited by (alphabeta-meATP appeared to be responsible for a non-selective cationic current. With internal application of low-molecular-weight heparin, a blocker of inositol 1,4,5-trisphosphate (InsP3), the oscillatory current elicited by UTP was abolished. The oscillatory current was activated in an all-or-none manner by UTP over the concentration range 0.1 and 1 microM and the frequency and amplitude were independent of the UTP concentration. Under current-clamp mode, UTP produced an oscillatory membrane potential. These results show that rat aortic myocytes have at least two types of P2 receptors. Activation of the P2Y receptor by UTP produces InsP3, which releases Ca2+ from the store site. The resulting increase in intracellular Ca2+ concentration causes the oscillatory Cl- current and the subsequent membrane potential changes.

Adenosine Triphosphate↗
PubMed1998

Ca2+ images and K+ current during depolarization in smooth muscle cells of the guinea-pig vas deferens and urinary bladder.

1. Electrical events and intracellular calcium concentration ([Ca2+]) imaged using fluo-3 and laser scanning confocal microscopy were simultaneously monitored in single smooth muscle cells freshly isolated from guinea-pig vas deferens or urinary bladder. 2. Images obtained every 8 ms, during stepping from -60 to 0 or +10 mV for 50 ms under voltage clamp, showed that a rise in [Ca2+] could be detected within 20 ms of depolarization in five to twenty small (< 2 micrometer diameter) 'hot spots', over 95 % of which were located within 1.5 micrometer of the cell membrane. Depolarization at 30 s intervals activated hot spots at the same places. 3. Cd2+ or verapamil abolished both hot spots and Ca2+-activated K+ current (IK,Ca). Caffeine almost abolished hot spots and markedly reduced IK,Ca. Cyclopiazonic acid, which raised basal global [Ca2+], decreased the rise in hot spot [Ca2+] and IK,Ca amplitude during depolarization. These results suggest that Ca2+ entry caused Ca2+-induced Ca2+ release (CICR). 4. Under voltage clamp, hot spot [Ca2+] closely paralleled the rise in IK,Ca and reached a peak within 20 ms of the start of depolarization, but the rise in global [Ca2+] over the whole cell area was much slower. Step depolarization to potentials positive to -20 mV caused hot spots to grow in size and coalesce, leading to a rise in global [Ca2+] and contraction. Ca2+ hot spots also occurred during the up-stroke of an evoked action potential under current clamp. 5. It is concluded that the entry of Ca2+ in the early stages of an action potential evokes CICR from discrete subplasmalemma Ca2+ storage sites and generates hot spots that spread to initiate a contraction. The activation of Ca2+-dependent K+ channels in the plasmalemma over hot spots initiates IK,Ca and action potential repolarization.

Action Potentials↗
PubMed1998

Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig.

Three major ionic currents, Ca2+-dependent K+ current (IK-Ca), delayed rectifier type K+ current (Ikd) and Ca2+ current (ICa), were activated by depolarization under whole-cell clamp in single smooth muscle cells isolated from guinea-pig urinary bladder. Externally applied ruthenium red (RuR) reduced the amplitude of IK-Ca and ICa at 0 mV (IC50 values were 4.2 and 5.6 muM, respectively), but did not affect IKd. Spontaneous transient outward currents (STOCs) and caffeine-induced outward currents (Icaf) at -30 mV were reduced by external 10 muM RuR. When 10 muM RuR was added to the pipette solution, IK-Ca during depolarization, STOCs and Icaf significantly decreased with time. RuR did not change the unitary current amplitude of the large-conductance Ca2+-dependent K+ (BK) channels, but reduced the open probability of the channel under excised patch-clamp recording mode. RuR reduced the channel activity more effectively from the cytosolic face than from the other. This inhibition decreased when the cytosolic Ca2+ concentration was increased. These results indicate that RuR blocks BK and Ca2+ channels in urinary bladder smooth muscle cells. The decrease in IK-Ca, STOCs and Icaf by RuR is attributable to the direct inhibition of BK channel activity, probably in addition to the inhibition of Ca2+ release from storage sites. The direct inhibition of BK channel activity by RuR may be related to the interaction of RuR with the Ca2+-binding sites of the channel protein.

Animals↗
PubMed1998

Comparative study of effects of isoproterenol and vasoactive intestinal polypeptide on voltage-dependent Ca2+ and Ca(2+)-activated K+ currents in porcine tracheal smooth muscle cells.

Effects of isoproterenol (Iso) and vasoactive intestinal polypeptide (VIP) on voltage-dependent Ca2+ channel (ICa) and Ca(2+)-activated K+ channel current (IK-Ca) in porcine tracheal smooth muscle cells were examined. When K+ currents were inhibited using a Cs-rich pipette solution, application of 0.1-1 microM Iso or 1-10 nM VIP increased ICa by 20-30%. On the other hand, IK-Ca elicited upon depolarization and spontaneous transient outward K+ currents (STOCs) recorded at a holding potential of -50 mV were enhanced by 80-100% in the presence of 0.1 microM Iso or 1 nM VIP.

Adrenergic beta-Agonists↗
PubMed1997

Effects of sematilide, a novel class III antiarrhythmic agent, on membrane currents in rabbit atrial myocytes.

The effects of sematilide, a novel class III antiarrhythmic agent, on membrane currents were examined in single myocytes isolated from the rabbit left atrium, using the whole-cell voltage clamp technique. Application of 10, 30, 100 and 300 microM sematilide caused a concentration-dependent inhibition of the delayed rectifier K+ current (IC50 approx. 25 microM). The sematilide-sensitive current, which was recorded by means of a triangular voltage command, showed a strong inward rectification and had a peak at about -40 mV, suggesting that sematilide inhibits the rapidly activating delayed rectifier K+ current. The Ca2+-independent transient K+ and the inward rectifier K+ currents were not affected significantly by application of 100 microM sematilide. Moreover, voltage-dependent Na+ and Ca2+ currents were not affected significantly by 100 microM sematilide. These findings indicate that sematilide selectively blocks the rapidly activating delayed rectifier K+ current in atrial myocytes and provide evidence supporting the usefulness of the drug as a class III antiarrhythmic agent.

Action Potentials↗
PubMed1997

Apamin-sensitive Ca2+-dependent K+ current and hyperpolarization in human endothelial cells.

Vascular endothelial cells have several types of Ca2+-dependent K+ current (I(K-Ca)). Here, we describe apamin-sensitive I(K-Ca) which is activated by treatment with histamine (His) in human umbilical vein endothelial cells (HUVECs). In 65 % of HUVECs examined, 100 nM apamin potently inhibited I(K-Ca) and hyperpolarization induced by His (19 and 7 % of control, respectively). In contrast, application of 5 mM tetraethylammonium, a non-selective K channel blocker, or 100 nM iberiotoxin, a selective K channel blocker for a large conductance Ca2+-dependent K+ channel, had small (78 % of control) or no effects (102 % of control) on I(K-Ca), respectively. These findings suggest that apamin-sensitive Ca2+-dependent K+ channels are expressed in HUVECs and activated by receptor stimulation.

Apamin↗
PubMed1997

Severe lactic acidosis and neonatal death in Pearson syndrome.

Pearson marrow-pancreas syndrome, a fatal disease associated with mitochondrial DNA rearrangements, is characterized by refractory sideroblastic anaemia during infancy. Only a few neonates with Pearson syndrome have been reported with metabolic acidosis. A female neonate who exhibited severe metabolic acidosis and anaemia at birth is described here. Her condition progressively worsened, with pancytopenia and uncontrollable metabolic acidosis resulting in death at the age of 14 days. A 4988-base pair deletion of mtDNA was detected in the patient's leukocytes, liver and muscle. When a neonate exhibits severe metabolic acidosis of unknown cause, the possibility of Pearson syndrome should be considered.

Acidosis, Lactic↗
PubMed1997

The association between haematological manifestation and mtDNA deletions in Pearson syndrome.

We studied the proportion of deleted mitochondrial DNA in blood cells from patients with Pearson syndrome. Patient 1 is a 17-year-old female with Kearns-Sayre syndrome who survived Pearson syndrome. Patient 2 is a 5-year-old boy with Pearson syndrome who recovered from refractory anaemia but continues to have thrombocytopenia and neutropenia. Patient 3 is a female neonate who died with severe acidosis and pancytopenia at 14 days of age. Southern blot analysis was performed with total DNA from three patients' blood cells and two samples of bone marrow cells from one patient. In peripheral blood, patients with a higher proportion of deleted mitochondrial DNA had lower blood cell counts. In patient 2, the percentage of mutant mitochondrial DNA in bone marrow cells decreased as anaemia improved. This indicates that the proportion of deleted mitochondrial DNA in peripheral blood and in bone marrow has a tendency to correlate to the severity of haematological manifestation.

Adolescent↗
PubMed1997

A case of an interstitial tandem direct duplication of long arm of chromosome 4: 46, XY, dup (4) (q25q31.3) de novo.

We report a 4 2/12-year-old Japanese boy with a de novo direct tandem dup (4) (q25q31.3). The major clinical picture includes postnatal growth and psychomotor retardation, thick eye-lashes, a cleft lip, and large and prominent helix and antitragus. He did not have any hearing deficit. His eyegrounds were normal. There was no organ malformations including brain, kidney, liver, pancreas, gallbladder, urinary bladder, stomach, and heart. Routine hematological tests, blood chemistry including thyroid hormones, and urinalysis including urinary screening tests for congenital metabolic disorders showed normal results. He showed an electroencephalographic abnormality which could have resulted from mild aseptic meningitis at 2 months. Our case supports the idea that the association of thumb and renal deformities in duplication 4q syndrome is related to the region 4q22-q23 as many researchers have already pointed out.

Child↗
PubMed1996

Time course of Ca(2+)-dependent K+ and Cl- currents in single smooth muscle cells of guinea-pig trachea.

The time course of two types of Ca(2+)-dependent currents were compared in single smooth muscle cells freshly isolated from guinea-pig trachea. When the pipette solution contained mainly 140 mM KCl, depolarization from -60 mV to 0 mV evoked an initial inward current followed by an outward current which consisted of transient (I(to)) and sustained components. In addition, a long-lasting inward tail current (Itail) was occasionally observed after the repolarization to -60 mV. Although I(to) often occurred repetitively during depolarization, the first I(to) reached the peak of approximately 50 ms after the start of depolarization and had the largest amplitude in most cells examined. The amplitude of Itail increased with the increase in depolarization period up to about 500 ms. Pharmacological analyses indicate that I(to) and Itail are Ca(2+)-dependent K+ and Cl- currents (IK-Ca and ICl-Ca), respectively, and suggest that not only Ca(2+)-influx through Ca2+ channels but also subsequent Ca2+ release from stores contributes to activate these currents. Spontaneous transient outward and inward currents, IK-Ca and ICl-Ca, respectively, were simultaneously recorded at -40 mV. In over 80% of the spontaneous current events, outward and inward currents coupled one to one and always occurred in this order. Puff-application of 10 mM caffeine also induced IK-Ca and ICl-Ca in this order at -40 mV. When caffeine was applied twice with various intervals, the current amplitude in the second application depended upon the period of the interval. The recovery of ICl-Ca during the interval was faster than that of IK-Ca. The results indicate that the activation and decay time courses of ICl-Ca are slower but its recovery is faster than those of IK-Ca.

Animals↗
PubMed1996

Effects of sematilide, a novel class III antiarrhythmic agent, on delayed rectifier K+ current in guinea pig atrial myocytes.

Effects of sematilide, a novel class III antiarrhythmic agent, on the delayed rectifier K+ current (Ik) were examined in guinea pig atrial myocytes using a voltage clamp technique. Sematilide inhibited both time-dependent outward current upon depolarization and tail currents (Ik-tail) at -40 mV. The concentration of sematilide required for a 50% decrease in Ik-tail was approximately 50 microM. The sematilide-sensitive current obtained using a triangular voltage command exhibited marked inward rectification and had the maximum amplitude at -30 mV. These results suggest that sematilide inhibits rapidly activating Ik in guinea pig atrial myocytes, resulting in the prolongation of action potential duration and refractoriness.

Action Potentials↗
PubMed1996

Effects of ONO-1101, a novel beta-antagonist, on action potential and membrane currents in cardiac muscle.

Direct effects of ONO-1101 ¿(-)-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-3-[4-[(S) -2-hydroxy-3-(2-morpholino carbonylamino)ethylamino] propoxy]phenylpropionate monohydrochloride), a novel beta-antagonist, on action potential parameters and membrane currents, and its beta adrenoceptor antagonism were examined in cardiac muscle. Action potential-parameters in papillary muscle of reserpinized animals and membrane currents recorded from single myocytes obtained from guinea pig and rabbit hearts were not affected by 1 to 100 microM ONO-1101. On the other hand, ONO-1101 markedly inhibited the potentiation of Ca current by isoproterenol in single cardiac myocytes of the guinea pig. The concentration-response relationship of Ca current for isoproterenol was shifted to the right. This effect resembled that of esmolol, which is also a beta adrenoceptor antagonist. A Schild plot analysis revealed the slope and pA2 value of each antagonist (ONO-1101, 0.94, 8.0; and esmolol, 0.98, 7.3, respectively) and demonstrated that ONO-1101 is about 5 times more potent than esmolol as a beta-antagonist. Two other effects of isoproterenol: 1) potentiation of delayed rectifier K current and 2) activation of chloride current, were also inhibited by ONO-1101. The time required for 50% removal of beta-antagonism of ONO-1101 and esmolol after the washout was estimated as 4 and 6 min, respectively, in depolarized papillary muscle. These results suggest that ONO-1101 is a potent beta-antagonist whose effects were removed quickly by washout. When applied at what is thought to be a clinical dosage, ONO-1101 had no direct effects on action potential-parameters and membrane currents in cardiac muscle. These characteristics of ONO-1101 suggest that this agent may be effective in clinical use.

Action Potentials↗
PubMed1996

Neutral endopeptidase activity in serum and cerebrospinal fluid.

We measured neutral endopeptidase (NEP) activity in serum from non-smoking healthy Japanese and in cerebrospinal fluid (CSF) from patients without neurological or inflammatory diseases. The serum NEP activity (sNEP) of 25 males and 25 females, aged 20 to 65 years, ranged from 0.003 to 1.62 pmole/min/microliter. There was no significant difference in sNEP activity between the sexes (male: 0.40 +/- 0.34 pmol/min/microliter vs female: 0.37 +/- 0.30, mean +/- S.D.). There was a significant positive correlation (p < 0.05) between sNEP and age. The NEP activity in the CSF (cNEP) ranged from 0.07 to 0.63 pmole/min/microliter. Male patients with benign prostate hypertrophy (BPH) showed cNEP activity of 0.21 +/- 0.11 pmol/min/microliter (n = 13), and female patients with myoma uteri (MU) or dysplasia of the uterus mucosa (DUM) showed activity of 0.32 +/- 0.20 (n = 5). There was no significant difference in cNEP activity between the sexes. Three patients with severe body pain showed cNEP activity of 0.21, 0.15, and 0.16 pmole/min/microliter, and these values were dissimilar from those of the BPH, MU, or DUM patients.

Age Factors↗
PubMed1995

Characteristics of caffeine-induced and spontaneous inward currents and related intracellular Ca2+ storage sites in guinea-pig tracheal smooth muscle cells.

Characteristics of caffeine-induced inward current (Icaf) and spontaneous transient inward current were examined in single smooth muscle cells isolated from guinea-pig trachea. When a pipette solution contained mainly CsCl, an application of 10 mM caffeine elicited transient Icaf at a holding potential of -60 mV. Spontaneous transient inward currents were recorded in about 15% of cells examined and were abolished by caffeine. Both were Cl- current activated by an increase in intracellular Ca2+ concentration (ICl-Ca). When 10 mM caffeine was puff-applied twice with various intervals, the amplitude of the second Icaf depended upon the period of the interval. The relationship between the amplitude and the interval represents the recovery time course of Icaf, which was significantly slowed by 30 microM cyclopiazonic acid. The Icaf was not significantly affected by addition of Cd2+. Removal of external Ca2+ did not affect the first Icaf but markedly reduced the second one, regardless of the presence of Cd2+. In conclusion, Icaf is evoked by activation of ICl-Ca via Ca2+ release. The recovery time course of Icaf indicates the refilling of Ca2+ storage sites by the cyclopiazonic acid-sensitive Ca2+ pump. The refilling at -60 mV depends strongly upon Ca2+ influx through the Cd(2+)-insensitive pathway. Spontaneous transient inward currents may be also due to ICl-Ca activated by spontaneous Ca2+ release from local storage sites.

Animals↗