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Biomedical subjects

N Iwatsuki

Publications and source records attributed to N Iwatsuki.

At least 73 records · Page 4Linked to original sources
PubMed1980

Inotropic effects of non-depolarizing muscle relaxants in isolated canine heart muscle.

The inotropic effects of five non-depolarizing muscle relaxants were examined using an isolated canine heart muscle preparation. Except for fazadinium, all drugs were studied in their commercially available forms. d-Tubocurarine chloride (dTc) and metocurine iodide (MTC) produced dose-dependent decreases in isometric force (F) and the maximum velocity of force development (dF/dt) at concentrations greater than 22.5 x 10(-3) g/L for dTc and greater than 15.0 x 10(-3) g/L for MTC, concentrations which are 3 and 6 times higher than estimated clinical serum concentrations, respectively. Myocardial depression was about 3 times less with MTC than with dTc at equipotent concentrations. The degree of depression in F and dF/dt produced by MTC was almost identical with that produced by phenol, a preservative of MTC, indicating that MTC-induced myocardial depression may be due to the effect of the preservative. Pancuronium bromide (PC) produced a dose-dependent increase in F and dF/dt and decrease in the time to peak force. PC-induced changes in F, dF/dt, and time to peak force were inhibited by administration of propranolol 10(-6) M. The results indicate that PC possesses a positive inotropic effect mediated by beta-adrenergic stimulation. Alcuronium chloride did not change F or dF/dt at concentrations from 5.0 x 10(-3) to 60.0 x 10(-3) g/L. Frazadinium bromide increased F and dF/ dt slightly at a low concentration (1.875 x 10(-2) g/L), but further increases in its concentration returned the values of F and dF/dt to control levels. F and dF/dt were not altered in vitro by concentrations of relaxants that would be anticipated in plasma in vivo in patients given clinically effective doses of 0.3 mg/kg of dTc, 0.1 mg/kg of MTC or PC, 0.2 mg/kg of alcuronium chloride, or 0.75 mg/kg of fazadinium bromide.

Alcuronium↗
PubMed1980

A weak negative inotropic effect of protamine sulfate upon the isolated canine heart muscle.

The direct effect of protamine sulfate upon myocardial inotropism was studied using an isolated canine heart muscle preparation. Isometric force (F) was decreased to 87.6 +/- 1.2% of control values by a concentration of 50 x 10(-3) g/L protamine, which is approximately equal to the estimated serum concentration of protamine when administered clinically in doses of 4 mg/kg. The decrease in F was accompanied by a decrease in the maximum velocity of force development (dF/dt) but no alteration in time to peak force. Administration of the preservative of protamine sulfate did not alter F and dF/dt. This suggests that protamine produces a direct negative inotropic effect, mediated by a decrease in intensity but not by a decrease in duration of the active state.

Animals↗
PubMed1979

Intracellular Ca2+ injection causes membrane hyperpolarization and conductance increase in lacrimal acinar cells.

Membrane potential and resistance measurements were carried out on segments of superfused mouse exorbital lacrimal glands by inserting two microelectrodes into neighbouring coupled cells. Short-lasting intracellular injections of Ca2+, by the method of microiontophoresis, caused membrane hyperpolarization and resistance reduction. These effects were also observed in the presence of adrenergie and cholinergic blocking agents. From the potential and resistance changes observed the null potential for the action of Ca2+ was calculated to be -50 mV. Short-lasting extracellular Ca2+ applications caused membrane hyperpolarization and resistance reduction, but these effects were blocked by a combination of atropine and phentolamine. Intracellular Ca2+ application mimics the action of adrenaline and acetylcholine on lacrimal acinar cells.

Acetylcholine↗
PubMed1979

Direct visualization of cell to cell coupling: transfer of fluorescent probes in living mammalian pancreatic acini.

A technique whereby it is possible directly to observe the movement of organic molecules from cell to cell in living mammalian exocrine glands is described. Thin translucent segments of mouse pancreas are mounted in a superfusion bath. Fluorescent probes are injected intracellularly via fine micropipettes and fluorescence observed. Both fluorescein (mol. wt. 332) and procion yellow (mol. wt. 697) are shown to be transferred from the injection cell to neighbouring acinar cells. This shows directly the existence of intercellular communicating pathways.

Animals↗
PubMed1979

Cardio-circulatory effects of enflurane anesthesia in health and disease.

The circulatory effects of enflurane (Ethrane) were studied in 10 unmedicated volunteers during anesthesia over a period of 90 min or more. Cardiac output did not change significantly at a mean alveolar concentration of 2.3 vol.%. Heart rate was increased in all cases. Enflurane causes negative inotropic activity in the heart muscle but has little influence on the pump performance of the heart.

Anesthesia, Inhalation↗
PubMed1979

Pancreatic acinar cells: the effect of carbon dioxide, ammonium chloride and acetylcholine on intercellular communication.

1. Segments of mouse pancreatic or exorbital lacrimal gland were superfused with saline solutions. Under visual control two micro-electrodes were inserted into neighbouring cells within the same acinus or into neighbouring acini. Cell to cell electrical coupling was assessed by injecting rectangular current pulses through one electrode and measuring the electrotonic potential change in the same cell (V(1)) and in the neighbouring cell (V(2)). Acetylcholine (ACh) was added locally to impaled acini by micro-ionophoresis from an extracellular micropipette.2. Exposure of the tissues to a Krebs solution equilibrated with 100% CO(2) caused a rapid increase in the size of electrotonic potential changes in the current injection cell and disappearance of the electrotonic potential changes in a neighbouring acinus or cell. This electrical uncoupling of previously coupled cells was rapidly reversible upon return to a solution equilibrated with 95% O(2) and 5% CO(2).3. Reduction of electrical intercellular coupling was also obtained using smaller CO(2) concentrations (50, 20 or 10%). In these cases the effects developed more slowly and were less dramatic. Reducing the extracellular HCO(3) concentration enhanced the uncoupling effect of 10 or 20% CO(2). However, weak uncoupling effects were still observed using 10 or 20% CO(2) in combination with a high bicarbonate concentration maintaining a constant extracellular pH (7.4).4. Reductions in extracellular pH (down to 5.5) achieved by varying combinations of Tris base and Tris HCl had no effect on electrical coupling. Brief periods of anoxia (100% N(2)) also had no effect.5. Exposure to 20% CO(2) markedly enhanced the uncoupling effect of a brief ionophoretic pulse of ACh.6. Exposure of the tissue to 10 mM-NH(4)Cl, a procedure expected to increase the intracellular pH, counteracted the uncoupling effect of ACh. During sustained uncoupling caused by a sustained ACh stimulation a brief period of exposure to NH(4)Cl caused an immediate and fully reversible recoupling.7. It is concluded that variations in intracellular pH have marked effects on the electrical coupling between neighbouring cells in the pancreatic and lacrimal acinar tissue.

Acetylcholine↗
PubMed1978

Intracellular Ca2+ injection causes membrane hyperpolarization and conductance increase in lacrimal acinar cells.

Membrane potential and resistance measurements were carried out on segments of superfused mouse exorbital lacrimal glands by inserting two microelectrodes into neighbouring coupled cells. Short-lasting intracellular injections of Ca2+, by the method of microiontophoresis, caused membrane hyperpolarization and resistance reduction. These effects were also observed in the presence of adrenergic and cholinergic blocking agents. From the potential and resistance changes observed the null potential for the action of Ca2+ was calculated to be -50 mV. Short-lasting extracellular Ca2+ applications caused membrane hyperpolarization and resistance reduction, but these effects were blocked by a combination of atropine and phentolamine. Intracellular Ca2+ application mimics the action of adrenaline and acetylcholine on lacrimal acinar cells.

Acetylcholine↗
PubMed1978

Parotid acinar cells: ionic dependence of acetylcholine-evoked membrane potential changes.

Segments of mouse parotid were placed in a superfusion chamber. Surface acini were impaled by one or two micro-electrodes for measurement of membrane potential and resistance. The acinus under investigation was stimulated by micro-iontophoretic application of acetylcholine (ACh) or adrenaline. Neighbouring acinar cells were electrically coupled. Electrical coupling between acinar cells only occurred within restricted domains probably corresponding to an acinus or a group of acini. Passing direct current through one intracellular electrode, the resting potential of an acinus could be set at desired levels and the dependency of the ACh-evoked potential change on the resting potential investigated. The ACh null potential (initial effect) was about--60 mV. A delayed hyperpolarizing effect of ACh could not be reversed. The initial ACh-evoked potential change was sensitive to alterations in extracellular Na, K and Cl concentration. The delayed ACh-evoked hyperpolarization was blocked by ouabain, exposure to Na-free or K-free solutions. It is concluded that ACh increases mainly K and Na membrane conductance causing K efflux and Na influx with a subsequent Na activation of an electrogenic Na pump.

Acetylcholine↗
PubMed1978

Electrical coupling and uncoupling of exocrine acinar cells.

The electrical communication network in the mouse pancreatic acinar tissue has been investigated using simultaneous intracellular recording with two separate microelectrodes and direct microscopical control of the localizations of the microelectrode tips. All cells within one acinus were electrically coupled, and the coupling coefficient (the electrotonic potential change in a cell neighboring to the cell into which current is injected [V2] divided by the electrotonic potential change in the cell of current injection [V1]) between two cells near each other (less than 50 micron) was always close to 1. Cells farther apart (50-100 micron) were, in some cases, coupled; in other cases, there was no coupling at all. Coupling coefficients varied between 0 and 1. There was rarely electrical coupling over distances of more than 110 micron. Using microiontophoretic acetylcholine (ACh) application, it was possible to evoke almost complete electrical uncoupling of two previously coupled pancreatic or lacrimal acinar cells from different acini or within one acinus. The effects were fully and quickly reversible. While the ACh-evoked uncoupling in the pancreas was associated with membrane depolarization, ACh caused hyperpolarization in the lacrimal acinar cells. The uncoupling was associated with a very marked reduction in electrical time constant, indicating a reduction in input capacitance (effective surface cell membrane area). The concentrations of stimulants needed to evoke reduction in pancreatic cell-to-cell coupling were 1 micron for ACh, 0.14 nM for caerulein, and 3 nM for bombesin. These concentrations are smaller than those required to evoke maximal enzyme secretion.

Acetylcholine↗
PubMed1978

Effect of thiamylal on the sensitivity of glycerinated cardiac fibres to calcium.

Clarification of the mechanisms of the myocardial depression produced by thiamylal was sought by studying the effect of thiamylal upon the sensitivity of contractile proteins to calcium (Ca2+), by using glycerinated muscle fibres from the canine right ventricle. The dose--response relationship between the concentration of Ca2+ and the force of contraction of the glycerinated cardiac muscle fibres was not shifted from the control curve by the administration of thiamylal 67 microgram ml-1. This result suggests that the changes in the sensitivity of contractile proteins to Ca2+ are not responsible for the depression of myocardial performance produced by thiamylal.

Animals↗
PubMed1978

Pancreatic acinar cells: acetylcholine-evoked electrical uncoupling and its ionic dependency.

1. Isolated segments of mouse or rat pancreas were placed in a Perspex bath through which physiological saline solutions were circulated. Intracellular recordings from surface acini were made by inserting up to three separate micro-electrodes into neighbouring cells within the same acinus. Through one of these electrodes current pulses could be injected. Electrical coupling between the cells could be continuously assessed. The acinus under investigation was stimulated by iontophoresis of ACh from an extracellular micropipette.2. During resting conditions all cells within an acinus were fully electrically coupled. A 5-10 sec pulse of a relatively large iontophoretic ACh ejecting current, causing initially the well characterized surface cell membrane depolarization and resistance reduction, was followed by a marked electrical uncoupling of neighbouring cells. In some cases one cell was clearly being isolated equally from the two other cells impaled, in other cases the cell into which current pulses were injected was becoming more isolated from one of the neighbouring cells than from the other one.3. The ACh-evoked electrical uncoupling was completely reversible and could be repeatedly observed in the same cell.4. The electrical uncoupling in response to short pulses of ACh (5-10 sec) was not affected by even prolonged (up to 50 min) exposure to Ca-free solution containing EGTA.5. ACh-evoked uncoupling (short pulses) was not reduced about 5 min after introduction of Mn (2 mM), Ni or Co (5 mM). Mn thereafter gradually reduced and finally (after about half an hour) abolished the ACh-evoked uncoupling. Ni and Co gradually enhanced the uncoupling response. The blocking effect of Mn on the ACh-evoked uncoupling occurred much faster in the absence of superfusion fluid Ca.6. During a period of sustained ACh stimulation sustained electrical uncoupling was observed. If Ni or Co (5 mM) was introduced during such a stimulatory period the cells recoupled. This effect of Ni and Co was immediate and fully reversible.7. The uncoupling responses to short pulses of ACh was not reduced immediately after replacing superfusion fluid Na by Tris at a time when the surface cell membrane depolarization and resistance reduction was already severely reduced. Thereafter a gradual slow reduction of the ACh-evoked uncoupling was observed. This did not occur if Na was replaced by Li.8. It is concluded that the Ca needed to raise [Ca(2+)](i) sufficiently to cause electrical uncoupling comes from the cells in cases of uncoupling evoked by short pulses of ACh, but from the external solution in cases of sustained uncoupling evoked by sustained stimulation of ACh.

Acetylcholine↗
PubMed1978

Membrane potential, resistance, and intercellular communication in the lacrimal gland: effects of acetylcholine and adrenaline.

1. Intracellular micro-electrode recordings were made from surface acini of mouse exorbital lacrimal glands placed in a Perspex bath through which oxygenated physiological saline solutions were circulated. Two micro-electrodes were inserted into neighbouring communicating cells. Through one of the electrodes, current pulses could be injected. The cells impaled were stimulated by iontophoresis of acetylcholine (ACh), adrenaline or isoprenaline from an extracellular micropipette. 2. During exposure to standard Krebs solution the resting membrane potential was -42.5 mV +/- 1.2 and the resting input resistance 3.3 Momega +/- 0.3. When the tips of the two intracellular micro-electrodes were more than 100 micrometer apart no electrical coupling between two impaled cells could be detected. At intertip distances below about 80 micrometer coupling was frequently observed. In all such cases the coupling ratio was 1. The resting current-voltage relation was almost linear within the membrane potential range of -30 to -80 mV. 3. During exposure to standard Krebs solution the resting membrane potential was -42.5 mV +/- 1.2 and the resting input resistance 3.3 Momega +/- 0.3. When the tips of the two intracellular micro-electrodes were more than 100 micrometer apart no electrical coupling between two impaled cells could be detected. At intertip distances below about 80 micrometer coupling was frequently observed. In all such cases the coupling ratio was 1. The resting current-voltage relation was almost linear within the membrane potential range of -30 to -80mV. 3. During exposure to standard Krebs solution short iontophoretic pulses of ACh or adrenaline caused fully reversible hyperpolarizations accompanied by marked reduction of surface cell membrane resistance and membrane time constant. The effects of ACh were blocked by atropine (1.4 x 10(-6)M). Iontophoresis of isoprenaline never had any detectable effect on membrane potential or resistance. 4. Applying de- or hyperpolarizing direct currents through one of the two intracellular micro-electrodes the effect of ACh or adrenaline could be observed at different lvels of resting potential. Depolarizing the acinar cell membrane resulted in an enhanced stimulant-evoked hyperpolarization whereas hyperpolarizing the acinar cell membrane resulted in a reduction, and at potentials more negative than -60 mV in a reversal of the stimulant-evoked potential change. The ACh equilibrium potential (EACh) under control conditions was -56.6 mV +/- 1.1 and EAdrenaline was -61.4 mV +/- 1.0. 5. Replacing the control superfusion solution by a Clfree sulphate solution resulted in an immediate shift of EACh towards more negative values. At steady state in the Cl-free solution the resting input resistance was 6.8 Momega +/- 1.3 EACh was -95.9 mV +/- 3.4. 6. Reducing [K]o from the usual 4.7 to 1.0 mM resulted in an immediate marked increase in the amplitude of ACh-evoked hyperpolarization whereas increasing [K]o to 10 mM almost abolished the ACh-evoked potential, but not resistance change. 7...

Acetylcholine↗
PubMed1978

In vitro action of bombesin on amylase secretion, membrane potential, and membrane resistance in rat and mouse pancreatic acinar cells. A comparison with other secretagogues.

Bombesin caused depolarization of rat or mouse pancreatic acinar cell membrane, reduction of membrane resistance, and a steep rise in amylase output from superfused pancreatic fragments. These effects were similar to those previously described for acetylcholine, cholecystokinin, and gastrin. The dose-response curves for these three effects of bombesin were very similar, with effects being detectable at concentrations of about 30 pM and maximal effects at about 10 nM. The equilibrium potential for the membrane action of bombesin, i.e., the membrane potential at which bombesin did not cause any change in membrane potential, was -16 mV. Similar values for equilibrium potential were obtained with acetylcholine, caerulein and pentagastrin. Bombesin in the higher dose range (10 nM) caused electrical uncoupling of acinar cells within an acinus, i.e., a marked increase in junctional membrane resistance. Similar uncoupling effects were observed after acetylcholine, caerulein, and pentagastrin stimulation. In conclusion, bombesin acts on the pancreatic acinar plasma membrane in exactly the same way as acetylcholine and cholecystokinin-pancreozymin. The electrical uncoupling caused by stimulation is evidence for an increase in cytosol free calcium ion concentration.

Acetylcholine↗