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Biomedical subjects

N Iwatsuki

Publications and source records attributed to N Iwatsuki.

At least 91 records · Page 5Linked to original sources
PubMed1977

The effects of gastrin and gastrin analogues on pancreatic acinar cell membrane potential and resistance.

1 Intracellular recordings of membrane potentials and input resistance have been made from the exocrine acinar cells of mouse and rat pancreas placed in a tissue bath perfused with Krebs-Henseleit solution.2 The resting acinar cell membrane potential was about -38 mV. The acinar cells were stimulated by cholecystokinin-pancreozymin (CCK-PZ), gastrin and the gastrin-related polypeptides, caerulein and desulphated caerulein. The immediate effect of stimulation with these secretagogues was always a depolarization and a concomitant reduction in input resistance and time constant. Depolarization of the acinar cell membrane by these secretagogues was not abolished in the presence of atropine (1.4 muM).3 These peptide secretagogues were divided into the gastrin group and the CCK-PZ group according to the time course of the depolarizations and the shape of the dose-response curve. The depolarization evoked by the gastrin group returned quickly to the resting level but that evoked by the CCK-PZ group was long lasting. The time course and the dose-response curve for desulphated caerulein was identical with that of gastrin.4 It was confirmed electrophysiologically that the activity of gastrin is exerted by the C-terminal tetrapeptide; but the activity of caerulein depends on the C-terminal heptapeptide, especially the presence in the molecule of the sulphated tyrosyl residue at position 7 (numbering from the C-terminus). The equivalent sulphated tyrosyl residue in CCK-PZ is probably necessary for optimal activity of this polypeptide.5 The dose-response curves obtained by electrophysiological methods indicated that the relative potencies of the peptides on mouse pancreatic acinar cells were caerulein > CCK-PZ > gastrin. Synthetic human gastrin I was found to have a higher potency than either tetra- or pentagastrin.

Acetylcholine↗
PubMed1977

Pancreatic acinar cells: localization of acetylcholine receptors and the importance of chloride and calcium for acetylcholine-evoked depolarization.

1. Intracellular micro-electrode recordings of acinar cell membrane potential and resistance were made from the mouse pancreas superfused in vitro. The acinar cells under investigation were stimulated by micro-iontophoretic ACh application from an extracellular AChCl-filled micro-electrode.2. Passing short-lasting ejecting current pulses through the AChCl-electrode caused acinar cell depolarization when the electrode was in an extracellular position not far (< 50 mum) from an acinus impaled by a KCl micro-electrode. After insertion of the AChCl electrode into a neighbouring acinar cell, electrically coupled to the acinar cell already impaled by the KCl-electrode, ejecting ACh current pulses only affected the membrane potential in a direct electrical manner whereas there was no sign of an effect of ACh on the membrane potential.3. Replacing extracellular chloride by sulphate caused a marked increase in the amplitude of the ACh-evoked depolarization. If the membrane potential was recorded with a KCl electrode ACh continued to evoke very large depolarizations even after more than 1 hr exposure to Cl-free solution. If the membrane potential was recorded with a K-citrate electrode the effect of Cl-removal was only transient. Removal of Na(+) during exposure to Cl-free solution reduced the amplitude of the ACh-evoked depolarization somewhat. Readmission of Cl after more than 1 hr of Cl deprivation caused an immediate reversal of the ACh effect into a hyperpolarization.4. Removal of extracellular Ca(2+) caused a marked reduction in the amplitude of small depolarizations evoked by just suprathreshold doses of ACh, whereas there was very little effect on larger depolarizations evoked by maximal or supramaximal ACh ejections. The effect of Ca removal was fully reversible. Addition of Mn after Ca-deprivation was as efficient as Ca in restoring normal electrophysiological responses to small doses of ACh.5. The acinar cell membrane seems only to be responsive to ACh added to the extracellular side and ACh probably causes an increase in membrane Cl permeability in addition to the previously described effects on Na and K permeability. Ca may be important in determining ACh receptor sensitivity.

Acetylcholine↗
PubMed1977

Pancreatic acinar cells: the acetylcholine equilibrium potential and its ionic dependency.

1. Two glass micro-electrodes were inserted into neighbouring cells from rat or mouse pancreatic segments, superfused in vitro. The tip of a third glass micro-electrode, filled with 2 M-AChCl, was placed just outside the acinus under investigation. Membrane potential and resistance, and changes in these parameters in response to short pulses of ACh stimulation, were recorded.2. The resting current-voltage relationship, obtained by injecting 100 msec depolarizing or hyperpolarizing current pulses through one of the intracellular micro-electrodes and recording the membrane potential with the other intracellular electrode, was linear within the range -5 to -60 mV.3. Injecting depolarizing or hyperpolarizing current (d.c.) through one of the intracellular micro-electrodes, the membrane potential (as measured with the other intracellular micro-electrode) could be set at various levels. The effect of ACh at different membrane potentials was investigated. When the acinar cell membrane was hyperpolarized, the amplitude of ACh-evoked depolarization was increased, while ACh-evoked depolarization was reduced when the membrane potential was reduced by depolarizing current, and finally changed into a hyperpolarization at very low membrane potentials. In each acinus investigated (rat and mouse), there was a linear relationship between amplitude of ACh-evoked potential change (DeltaV) (+ value or - value according to polarity) and resting membrane potential. During superfusion with control solution, the value of the membrane potential at which ACh did not evoke a potential change (E(ACh)) was about -15 mV in the mouse and about -20 mV in the rat. During superfusion with a chloride-free sulphate-containing solution (steady state), a linear relationship between DeltaV and resting membrane potential was again found but E(ACh) (mouse) was about +10 mV.4. A continuous rough estimate of E(ACh) was obtained by injecting repetitively depolarizing current pulses (100 msec) through one intracellular micro-electrode; in this way, the effect of ACh measured by the other intracellular electrode could be assessed simultaneously at the spontaneous resting level, and at a depolarized level. The direction of change in E(ACh) following acute changes in the superfusion fluid ion composition was assessed. Replacing extracellular chloride by sulphate caused an immediate change in E(ACh) in the positive direction. Re-admission of chloride, after a long period of chloride ion deprivation, caused an immediate sharp change in E(ACh) in the negative direction. Replacing extracellular sodium by Tris caused an immediate transient negative change in E(ACh). In contrast, taking away extracellular calcium changed E(ACh) in a positive direction. Augmenting extracellular potassium concentration to 40 mM caused a change in E(ACh) in the positive direction.5. At a membrane potential (V) equal to E(ACh) the sum of ionic currents evoked by the action of ACh is zero. Using the Goldman treatment, it appears that ACh increases membrane Na, K and Cl permeability. The approximate relative ion permeabilities of the pathways opened up by ACh are: P(Na)/P(K) = 2.5 and P(Cl)/P(K) = 5. At V = E(ACh), the approximate relative sizes of the ACh-evoked currents are: I(Na)/I(K) = 2.6 and I(Cl)/I(K) = 1.6 ACh, therefore, causes influx of Na and Cl and a small efflux of K.

Acetylcholine↗
PubMed1976

Effects of change in concentration of calcium on myocardial contractility depressed by thiamylal and halothane.

The effects of change in the concentration of Ca++ on myocardial contractility depressed by thiamylal and halothane were studied in isolated dog heart muscle. The concentration of Ca++ in the bathing medium was increased stepwise from 1.9 to 20.9 mM. An increase in Ca++ concentration resulted in an increase both in net-shortening (delta1) and in maximum velocity of shortening at 0.4 g preload (V'max) which reached the maximum values at 11.4mM of Ca++. A further increase in Ca++ concentration rather decreased delta1 and V'max. The concentration-response relation curves in the presence of thiamylal (3.3 mg%) shifted to the right almost parallel to the control curve, with the peaks at 15.2 mM of Ca++. The result indicates that the depression of myocardial contractility produced by thiamylal is counteracted competitively by Ca++. However, the curves in the presence of halothane (5.0 +/- 0.4 mg%) were kept lower than those of the control, with the peaks at 7.6 mM of Ca++. The result shows that the counteraction of Ca++ to the depression of myocardial contractility was limited in the presence of halothane. A similar tendency was observed in maximum force of isometric contraction (Fm). Moreover, in the presence of halothane, the administration of higher concentrations of Ca++ almost always accompanied "after-contraction". From the result obtained and the literature concerned it was suggested that the mechanism for producing the depression of myocardial contractility might be different between thiamylal and halothane in relation to Ca++ movements at the Ca++ storage sites within the myocardium.

Animals↗
PubMed1975

Effects of change in frequency of stimulation on myocardial depression produced by thiamylal and halothane.

The effects of change in the frequency of stimulation on the myocardial contractility depressed by thiamylal and halothane were studied in isolated dog heart muscle. An increase in the frequency of stimulation from 0.1 to 0.6 cps resulted in a progressive in increase in net-shortening (delta1) and maximum velocity of shortening at 0.4 g preload (V'max), namely a positive staircase. The myocardium previously depressed to a similar degree by thiamylal or halothane still showed a positive staircase. This result indicates that the mechanism to produce the myocardial depression by thiamylal or halothane is not a complete inhibition of Ca++ influx across the cell membrane. The time to reach a steady state of contraction following an increase in the frequency of stimulation was longer in the presence than in the absence of these anesthetics. The degree of recovery from the myocardial depression by increasing the frequency of stimulation was much higher in the presence of thiamylal than in the presence of halothane. This fact suggests that the mechanism to produce the myocardial depression may be different in there two anesthetics.

Animals↗