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T Kiyosue

Publications and source records attributed to T Kiyosue.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Variations of dentition in raccoon dogs (Nyctereutes Procynoides Viverrinus T.) Anomalies in number of the teeth].

A study on the number of anomalous teeth was made by using gross and radiographic examinations on 179 skulls (male: 68, female: 53, unknown: 58) of raccoon dogs (Nyctereutes Procynoides Viverrinus T.) captured in the northern part of Kyushu. Results were as follows: 1. 8 skulls had 15 supernumerary teeth. They were in the upper incisor, the upper third premolar and the upper and lower first premolar regions. 2. 35 skulls had 58 congenitally missing teeth. Most of them were upper and lower first premolars or lower third molars. 3. One skull had one supernumerary tooth in the upper second incisor region and one congenitally missing tooth, a lower third molar. 4. The anomalous teeth were about 25%, the supernumerary teeth and congenitally missing teeth were about 4.5% and 20% respectively.

Animals↗
PubMed1986

Comparison of the inhibitory effects of mexiletine and lidocaine on the calcium current of single ventricular cells.

Effects of mexiletine and lidocaine on inward calcium current (ICa) of single ventricular myocytes from guinea pigs were studied using tight seal whole cell clamp method. Mexiletine at the concentrations of 10, 30 and 100 microM decreased ICa by 23.0, 28.9 and 55.4%, respectively, while lidocaine decreased it by 8.9, 16.8 and 25.2%. At all concentrations tested, a potency for ICa inhibition in mexiletine was significantly greater than that in lidocaine (p less than 0.05). The results suggest that mexiletine has, at therapeutic concentrations, a considerable blocking action on the Ca channels other than well-known action on the Na channels.

Action Potentials↗
PubMed1986

Effects of lysophosphatidylcholine on resting potassium conductance of isolated guinea pig ventricular cells.

We studied the effects of lysophosphatidylcholine (LPC), a toxic metabolite of ischemia, on the inward rectifier potassium channel current in isolated guinea pig ventricular cells. LPC (10-50 microM) added to the external solution decreased the resting membrane potential and occasionally induced repetitive action potential discharges, with or without loss of repolarization. In voltage clamp studies, LPC (20 microM) decreased the conductance at the levels of resting potentials (approximately equal to -80 mV) from 26 +/- 8 nS to 16 +/- 3 nS (mean and SD, n = 4) within 10 min. Prolonged application of LPC (greater than 12 min) produced transient inward currents after depolarizing clamp pulses, thereby suggesting that the LPC elevated intracellular Ca2+ concentrations. The effect of LPC on the single inward rectifier K channel current was examined using the patch clamp technique in a cell-attached mode. LPC decreased the single channel conductance, depending on the concentration (5-100 microM). The slope conductance in the presence of 150 mM K+ in the pipette decreased from 45 +/- 7 pS (control) to 32 +/- 17, 20 +/- 19, and 14 +/- 10 pS for 5, 20 and 100 microM LPC, respectively. LPC induced little change with regard to probability of the channel opening. These results suggest that LPC depolarizes membrane by decreasing single channel conductance of the inward rectifier K channel. This reduction partially contributes to the alleged LPC-induced abnormal automaticities and conduction disturbances in the heart.

Animals↗
PubMed1986

Effects of trimetazidine on action potentials and membrane currents of guinea-pig ventricular myocytes.

The effects of trimetazidine on membrane potentials and membrane currents of enzymatically isolated guinea-pig ventricular cells were studied with the use of giga-seal suction pipettes for patch clamp. Trimetazidine (3 X 10(-5) M) decreased the action potential duration from 433 +/- 179 ms (mean and S.D., n = 9) to 319 +/- 156 ms within 8 mins. In voltage clamp experiment, trimetazidine at a concentration of 1.5 X 10(-4) M decreased the peak amplitude of calcium current by 40% (0.92 +/- 0.46 nA to 0.55 +/- 0.19 nA, mean +/- S.D., n = 5). The effect on calcium current was rate-dependent, e.g., at 1 Hz, trimetazidine blocked a larger fraction of the calcium current than at 0.2 Hz. The drug decreased the conductance of potassium current which flows via inward rectifier potassium channel from 28 +/- 11 nS to 19 +/- 10 nS, n = 5, P less than 0.05). Trimetazidine shifted the steady state current-voltage relationship outward at potentials positive to -20 mV. This shift was not due to the enhanced time- and voltage-dependent outward current (Ik). From these findings, it was concluded that trimetazidine shortens action potential duration by blocking the calcium channels with increases in steady state outward current or a possible blockade of non-inactivated component of the calcium current, at the plateau potentials. The reduction of calcium current and of inward rectifier potassium current may protect the cardiac cells from accumulation of calcium ions and from loss of potassium ions, in the presence of ischemia.

Action Potentials↗
PubMed1986

Na,K-ATPase activity and repolarization of ventricular action potentials in simian hearts.

We measured Na,K-ATPase activity and ATP content of 4 different areas of the left ventricular muscle of Japanese monkeys (Mucaca fuscata): The apex, base, and epicardium (Epi) and endocardium (Endo) of the free wall. We compared those values with electrical parameters such as action potential duration (APD) and the level of resing potentials. APDs of base and Endo were significantly longer than those of apex and Epi, respectively. There was no significant difference in ATP contents among the four tissues while Na,K-ATPase activity in Epi was significantly higher, thereby indicating that the maximum capacity of the Na,K-pump activity is greater in Epi than in Endo. This observation serves to explain the following differences in electrophysiology characteristics found between Epi and Endo: greater shortening of APD in Endo when the cycle length of stimulation was shortened (from 2,000 to 200 ms) or when ouabain (0.5-1 microM) was applied; larger amplitude of post-overdrive hyperpolarization in Epi; and marked ouabain-induced depolarization of the resting potential in Endo, as compared to Epi. We conclude that the difference in Na,K-ATPase activity accounts for the different electrical behavior observed in Epi and Endo of the simian ventricle.

Action Potentials↗
PubMed1986

Overcoming drug resistance in cancer cells with synthetic isoprenoids.

A cultured subline (P388/ADM) of mouse P388 leukemia resistant to doxorubicin, vinblastine, vincristine, dactinomycin, and daunorubicin became sensitive again when treated with noncytotoxic doses of either of two synthetic isoprenoids: N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB-ethylenediamine) and N-(p-methylbenzyl)decaprenylamine X HCI (PMB-decaprenylamine). The isoprenoids also reversed resistance to doxorubicin and vincristine in a cultured vincristine-resistant P388 leukemia subline (P388/VCR). Median lethal doses (LD50) for PMB-decaprenylamine and SDB-ethylenediamine administered ip were 123 and 350 mg/kg against mice, whereas the LD50 for verapamil, another modifier of cellular drug resistance, was about 7.6 mg/kg. In vivo experiments with P388/VCR-bearing mice showed that both SDB-ethylenediamine and verapamil overcame vincristine resistance, but PMB-decaprenylamine showed only slight activity. SDB-ethylenediamine was especially effective, overcoming the vincristine resistance at 1 mg drug/kg. Since the structure of SDB-ethylenediamine resembles that of verapamil, a calcium-blocking agent that overcomes drug resistance, it was checked for calcium-blocking activity. However, calcium channel-blocking activity was not observed with 20 micrograms isoprenoid/ml, whereas calcium channel activity was completely blocked by 1 microgram verapamil/ml.

Animals↗
PubMed1985

Isoproterenol inhibits residual fast channel via stimulation of beta-adrenoceptors in guinea-pig ventricular muscle.

When perfused with high K+ (8.1 to 14.9 mM)-Tyrode's solution, the upstroke of action potentials in the isolated guinea-pig ventricular muscle is composed of two components and there are two separable peaks in the first derivative, i.e., Vmax, fast and Vmax, slow. The Vmax, fast was a measure of activation of the residual fast channel, while the Vmax, slow was that of the slow channel. Isoproterenol depressed Vmax, fast with increase in Vmax, slow, in a concentration-dependent manner (10(-8) to 10(-6) M). This depression of Vmax, fast was greater at more depolarized levels of membrane potential. Therefore, the isoproterenol-induced depression of Vmax, fast may be due to a negative shift of the curve relating Vmax, fast to the take-off potential (Em) (Vmax--Em relationship), along the voltage axis. The negative shift of Vmax--Em relationship by isoproterenol was also recognized in small preparations the size of which is well within the space constant. The negative shift was inhibited in the presence of beta-blockers (pindolol 1 microgram/ml or atenolol 10 micrograms/ml) but not by a calcium antagonist, 1-verapamil (1 microgram/ml). These results suggest that isoproterenol blocks sodium channels in the depolarized ventricular muscle via stimulation of the beta-adrenoceptors and that the depression of Vmax, fast is not mediated by the well-known effects of isoproterenol on Vmax, slow, i.e., increased influx of Ca2+ ions.

Action Potentials↗
PubMed1984

Lysophosphatidylcholine decreases single channel conductance of inward rectifier K channel in mammalian ventricular myocytes.

Effect of lysophosphatidylcholine (LPC) on the inward rectifier K channel of the isolated guinea pig ventricular cell was studied using patch clamp technique. In that LPC (100 microM) decreased the magnitude of the single channel conductance from 48 +/- 5 pS (mean and S.D., n = 5) to 12 +/- 9 pS (n = 8), this event may be the prime factor related to the alleged LPC-induced depolarization of cardiac tissues.

Animals↗
PubMed1983

Nature of "residual fast channel" dependent action potentials and slow conduction in guinea pig ventricular muscle and its modification by isoproterenol.

The nature of "residual fast channel" dependent action potentials and conduction was studied in guinea pig ventricular papillary muscle in which the resting potential was reduced to 58 +/- 1 mV in high K+ (16.7 mM) Tyrode's solution, with or without isoproterenol (0.1 microM). In the absence of isoproterenol, the action potential had a slur on the upstroke and the maximum rate of rise (Vmax) was composed of 2 separable peaks: the early large (32 +/- 7 V/s, Vmax,fast) and the late small (10 +/- 2 V/s, Vmax,slow) ones. The conduction velocity ranged from 30 to 35 cm/s. The Vmax,fast was selectively depressed by l-verapamil (1 microgram/ml), indicating that the impulses were transmitted through incompletely inactivated ("residual") fast channels. Lidocaine (2 micrograms/ml) depressed Vmax,fast with reduction of conduction velocity to about 20 cm/s just before the conduction block. Isoproterenol quadrupled the Vmax,slow but decreased Vmax,fast. As a result, the Vmax,slow overrode the Vmax,fast without change in the conduction velocity. In the absence of isoproterenol, there was no rate-dependent change in the action potential duration and the effective refractory period among the rates of 0.1, 0.5, and 0.9 Hz. Isoproterenol produced rate-dependent shortening in action potential duration with rate-independent shortening of postexcitation refractoriness, thereby resulting in a significant shortening in the effective refractory period at faster rates (0.5 and 0.9 Hz). Results suggest that the "residual fast channel" could produce "slow conduction" and that the ionic channels (fast or slow) responsible for the slow conduction may alternate according to local concentrations of tissue catecholamines.

Action Potentials↗
PubMed1983

Modification of "depressed fast channel dependent slow conduction" by lidocaine and verapamil in the presence or absence of catecholamines--evidence for alteration of preferential ionic channels for slow conduction.

We studied, with microelectrodes, the effect of lidocaine and 1-verapamil on the upstroke phase of action potentials and conduction velocity in incompletely depolarized ventricular papillary muscle (resting potential, -58 +/- 1 mV) perfused in a high K+ (16.7 mM) Tyrode's solution. The action potential upstroke had a slur and the maximum rate of rise (Vmax) consisted of 2 components: the first large (32 +/- 7 V/sec; Vmax,fast) and the second small (10 +/- 2 V/sec, Vmax,slow). The conduction velocity was slow and ranged about 30-35 cm/sec. Isoproterenol and noradrenaline increased Vmax,slow and decreased Vmax,fast, in a concentration dependent manner (10(-8) - 10(-5)M). These effects were abolished by following application of a beta-blocker, pindolol (1 microgram/ml). Thus, the dominant ionic channel responsible for the slow conduction seemed to alter from the depressed fast channel to the slow channel as the catecholamine concentration was increased. In the absence of isoproterenol, lidocaine (2 micrograms/ml) depressed Vmax with a resultant decrease of conduction velocity to 16.4 +/- 4.2 cm/sec and which was followed by a conduction block, while 1-verapamil was without effect. In the presence of isoproterenol (5 x 10(-7) M), 1-verapamil (1 microgram/ml) depressed the Vmax and decreased the conduction velocity to 16.9 +/- 4.2 cm/sec, just before development of the conduction block, while lidocaine was without effect. These results suggest that the dominant ionic channel responsible for the slow conduction in high K media (16.7 mM), can be readily altered by changes in extracellular catecholamine concentrations and that the slowest possible conduction velocity was approximately the same (about 16 cm/sec) between the depressed fast channel-dependent and the slow channel-dependent conductions. Clinical implications of these findings were discussed.

Action Potentials↗
PubMed1983

Electrocardiogram and His bundle electrogram of Japanese monkeys (Macaca fuscata).

Electrocardiogram (ECG) was taken from Macaca fuscata in the supine position under secobarbital anesthesia. The ECGs were recorded in the leads of standard (I, II, III), augmented unipolar limb (aVR, aVL, aVF) and unipolar chest (V4R, V1, V2, V3, V4, V5, V6,). The ECG was similar to that of humans as well as the monkeys of other species in their general patterns and the voltage of each wave (P, Q, R, S, T), though the heart rate was considerably different. The direction of T wave was consistent with that of human ECG. The PR, QRS and QT intervals and the duration of P wave were in good agreement with those of monkeys of other species, and amounted to about 50% of those of human ECG. His bundle electrogram (HBE) was recorded with a tripolar electrode catheter inserted into the right ventricle via the femoral vein, and PA, AH, HV and PV intervals were measured. All of the values were also approximately 50% and PV intervals were measured. All of the values were also approximately 50% of those reported in human HBE. Such short time intervals observed in Macaca fuscata may be due to a smaller heart size of the monkey as compared to the human's. The measurements of ECG and HBE reported in the present study may be used as a normal reference in ECG and HBE of Macaca fuscata under anesthesia. The study suggests that the Macaca fuscata is useful as an animal model to investigate the repolarization process of human ECG.

Animals↗
PubMed1983

Single channel analysis of the inward rectifier K current in the rabbit ventricular cells.

The inward rectifier K channel in rabbit ventricular cells was studied by the patch-clamp method. Single channel currents were recorded in giga-sealed cell-attached patches with 150 mM K+ in the pipette. The slope conductance in the membrane potential range from -140 to -40 mV was 46.6 +/- 6.7 pS (mean +/- S.D., n = 16), and was reduced by decreasing [K+] in the pipette (20 or 50 mM). The channel was blocked by an application of Cs+ or Ba2+ (0.04-1 mM) in the pipette. Outwardly directed current, recorded with 50 mM K+ in the pipette, revealed the inward rectification of the single channel current. The probability of the channel being open was 0.33 +/- 0.05 (n = 10) at the resting potential (RP=-81.7 +/- 1.7 mV, n = 16) with 150 mM K+ in the pipette, and it decreased with hyperpolarization. The mean open time of the channel was 178 +/- 25 msec (n = 6) at RP. The closed time of the channel seemed to have two exponential components, with time constants of 11.0 +/- 2.0 msec and 1.92 +/- 0.52 sec (n = 6) at RP. The slower time constant was increased with hyperpolarization. The averaged patch current recorded upon hyperpolarizing pulses demonstrated a time-dependent current decay as expected from the single channel kinetics. The results indicated that the inward rectifier K+ current has time- and voltage-dependent kinetics.

Animals↗
PubMed1983

Na, K-ATPase activity, ATP and Pi concentrations in various regions of monkey heart and their relation to post-overdrive hyperpolarization.

The relationship among Na, K-ATPase activity, ATP and inorganic phosphate (Pi) concentrations in functionally different regions of cardiac and skeletal muscles were studied in the Japanese monkey (Macaca fuscata). The activity of Na, K-ATPase was determined by the method of FIske and SubbaRow, and the concentrations of ATP and Pi, by isotachophoresis. The ATP concentrations in several regions of cardiac and skeletal muscles correlated positively with the Na, K-ATPase activities and Pi concentrations, whereas there was no significant correlation between the Na, K-ATPase activities and the Pi concentrations. Therefore, the ATP concentrations in functionally different regions of the tissues seemed to be a feasible measure of Pi concentrations and the Na, K-ATPase activities. The Na, K-ATPase activity was significantly higher in the epicardium than in the endocardium of the ventricle. The post-overdrive hyperpolarization was compared in these two tissues, using microelectrode methods. The hyperpolarization which followed overdrive stimulation (3.3-3.8 Hz) in the epicardium exceeded that in the endocardium, and was attributed to the difference in Na, K-ATPase activity. Our findings suggest that tissues with a higher Na, K-ATPase activity may have a more potent Na, K-pump activity, in association with higher tissue concentrations of ATP and Pi.

Adenosine Triphosphate↗
PubMed1983

Effects of SG-75 (nicorandil) on electrical activity of canine cardiac Purkinje fibers: possible increase in potassium conductance.

The effects of various concentrations (1-1000 microM) of SG-75 nitrate or nicorandil) were investigated in action potentials of canine Purkinje fibers with microelectrodes. In normal fibers stimulated at the standard cycle length of 1500 msec, the drug (1-100 microM) produced dose-dependent shortening in action potential duration without changes in the resting potential, the maximum rate of rise of phase 0 and the slope of phase 4 depolarization. The drug-induced percentage of shortening in the action potential duration was more pronounced at lower rates of stimulation and lower external K+ concentrations, but the shortening was unchanged in lower external Na+ concentrations. Depolarizations produced by Ba++ (0.04 mM) and low K+ (less than or equal to 1.35 mM) solution were partially reversed by the drug, whereas there were no effects on the high K+ (5.4-24.7 mM)-induced depolarizations. Stretch-induced depolarization was also partially recovered in the presence of the drug. SG-75 shortened the duration of the slow response produced by isoproterenol (1 microM) in the presence of 24.7 mM K+, with little change in the maximum rate of rise. We concluded that SG-75 increases membrane K+ conductance in cardiac Purkinje fibers probably by modifying ix1 and iK1 channels without changing the slow inward currents and that the effects are not mediated by muscarinic receptors. The computed action potentials indicated that this view was reasonable.

Action Potentials↗
PubMed1982

Electrophysiological and inotropic effects of Coenzyme Q10 on guinea pig ventricular muscle depolarized by potassium under hypoxia.

The electrophysiological and inotropic effects of Coenzyme Q10 (CoQ10) on isoproterenol or barium-induced slow responses in ventricular papillary muscle, depolarized by high K+ concentration (21.6 mM) under hypoxia (PO2 = 40 mmHg), were studied with microelectrode techniques. For the isoproterenol-induced slow response, application of CoQ10 (50 micrograms/ml), which was emulsified with the aid of a special solvent, increased the maximum rate of rise of action potentials (Vmax), an indicator of the slow inward current, by about 40%, with no consistent effect on the action potential duration and developed tension. Application of the solvent alone produced a significant decrease in both Vmax and developed tension. However, in these solvent-pretreated preparations, CoQ10 produced a significant (by about 50%) recovery in both Vmax and developed tension. The action potential duration was not changed by either the solvent alone or the application of CoQ10. The developed tension of the slow response consisted of early and late components. CoQ10 produced significantly more recovery in the late component than in the early one, suggesting that the recovery effect was due to increased slow inward Ca2+ current. CoQ10 did not reverse any parameter in the slow response induced by BaCl2 (0.2 mM). The results suggest that CoQ10 has significant but limited reversing effects on the hypoxia-induced deterioration of the slow response, and that the recovery is presumably due to increased availability of slow channels via increased production of ATP.

Action Potentials↗