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E K Matthews

Publications and source records attributed to E K Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1975

Electrical characteristics of pancreatic islet cells.

1. The electrical properties of mouse pancreatic islet cells have been explored in vitro using a single intracellular micro-electrode for both voltage recording and current injection. 2. The frequency of spontaneous electrical activity induced in islet cells by concentrations of D-glucose greater than 2-8 mM was enhanced by depolarizing, and reduced by hyperpolarizing, current injection. Post-stimulus inhibition and facilitation were also observed. 3. Intracellular current injection evoked a spike potential in Krebs solution containing a low D-glucose concentration (2-8mM), and in glucose-free, but not Ca-free solution. Evoked spikes were observed in approximately 10% of the cell population impaled. 4. The relationship between the rate of rise of an evoked spike and membrane potential displacement by intracellular current injection a sigmoid curve suggesting the presence of an inactivation process in spike potential genesis. 5. High [K]o, 30-50mM, induced electrical activity rarely, and then only transiently, thereafter blocking it; conditioning hyperpolarizing current tended to restore spike activity. 6. D-600, 5 times 10-minus 5M, blocked the electrical activity induced by D-glucose, tolbutamide or current injection; these inhibitory effects were reversed by a threefold increase in [Ca]o to 7-68 mM. 7. From these results it is concluded that the electrical activity induced in islet cells by Dglucose, tolbutamide and current injection is due mainlu to Ca-2+ influx and is dependent on the level of the membrane potential

Action Potentials↗
PubMed1975

Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity.

1. The effects of monosaccharides, glycolytic intermediates, metabolic inhibitors and anxia, have been studied on the membrane electrical activity of mouse pancreatic islet cells in vitro using a single intracellular micro-electrode for both voltage recording and current injection. 2. In addition to D-glucose (28mM), D-mannose (16-6mM), and L-leucin (10mM), the substances D-glyceraldehyde (11mM), and acetoacetate (20 mM), induced action potentials in islet cells but other glucos analogues and metabolic intermediates including L-glucose dod not. 3. Mannoheptulose 20 mM), but not D-galactose or 2-deoxy-D-glucose, antagonized the electrical activity induced in islet cells by D-glucose, 28mM. Prior treatment of the cells with mannoheptulose caused them to hyperpolarize and completely prevented the appearance of electrical activity on subsequent exposure to D-glucose. 4. Electrical activity induced by D0glucose 28mM, was progressively inhibited by phloridzin, 10mM, if the cells were exposed to D-glucose and inhibitor simultaneously, and abolished on pretreatment with inhibitor for 30-60 min. Phloridzin also caused depolarization of the islet cells which was independent of extracellular glucose. 5. Anoxia completely blocked the electrical activity induced by glucose but not that evoked by D-glyceraldehyde, L-leucine, tolbutamide or glibenclamide. 6. Iodoacetic acid, 5 mM, rapidly blocked glucose-induced electrical activity whilst that elicited by tolbutamide was relatively resistant to inhibition. 7. The nature and possible location of the glucoreceptor in pancreatic islet cells is discussed in relation to the origin and functional significance of glucose-induced electrical activity and insulin secretion.

Acetoacetates↗
PubMed1974

Calcium-ion binding to the chromaffin-granule surface.

1. Ca(2+) ions decreased the surface charge of isolated adrenal-medullary chromaffin granules whether the granules were untreated or previously incubated with neuraminidase. 2. Ca(2+) binding in both cases followed a Langmuir adsorption isotherm. 3. The chromaffin-granule surface was essentially polyanionic with about 10800 anionic sites per granule, of which 4200 sites are capable of binding Ca(2+) ions with an electrochemical free energy of adsorption of -1.32kJ.mol(-1). 4. The surface region of the chromaffin granule was calculated to bind 1306 Ca(2+) ions at 2.2mm-Ca(2+) (ionic strength 0.16mol.litre(-1)). 5. The importance of Ca(2+) binding to the chromaffin-granule surface is discussed in relation to the hypothesis of secretion by exocytosis.

Adrenal Medulla↗
PubMed1973

Pancreatic acinar cells: ionic dependence of the membrane potential and acetycholine-induced depolarization.

1. Intracellular recordings of membrane potentials have been made in vitro from the exocrine acinar cells of the mouse pancreas using glass micro-electrodes.2. The mean membrane potential of the acinar cells during superfusion with Krebs-Henseleit solution was -39.2 mV. Increasing [K](o) tenfold decreased the membrane potential by 28 mV when [K](o) was above 10 mM. This depolarization was not affected by atropine (1.4 x 10(-6)M). Strophanthin-G (10(-3)M) slowly depolarized the cells at about 10 mV hr(-1).3. Brief exposure to acetylcholine (ACh), 5.5 x 10(-5)M, or pancreozymin resulted in a short lasting depolarization of the acinar cells. Atropine (1.4 x 10(-6)M) blocked the depolarizing action of ACh but not that of pancreozymin. Adrenaline (5.5 x 10(-5)M) or cyclic AMP (10(-3)-10(-4)M) did not influence the membrane potential.4. The amplitude of the ACh-induced depolarization was not dependent on the presence of CO(2)/HCO(3) in the bathing fluid, but it was closely dependent on the extracellular Na concentration. However, ACh was still able to evoke a small depolarization even after prolonged exposure of the tissue to a Na-free solution.5. During exposure of the tissue to a Ca-free solution the resting membrane potential was decreased and the ACh-induced depolarization was significantly reduced. Some substances which are known in other tissues to inhibit membrane Ca(2+) currents, i.e. La(3+), D-600 and tetracaine, were able to reduce, but never abolish, the ACh-induced depolarization.6. These results suggest that the effect of ACh on the pancreatic acinar cell is to increase the permeability of the membrane to commonly occurring ions with a consequent Na-influx and a small Ca-influx.

Acetylcholine↗
PubMed1973

Ionic dependence of adrenal steroidogenesis and ACTH-induced changes in the membrane potential of adrenocortical cells.

1. The effects of changes of ionic environment upon corticosteroid production by rabbit adrenal glands have been investigated in vitro using a superfusion technique and on-line steroid analysis by an automated fluorescence method. In some experiments micro-electrode recordings of adrenocortical transmembrane potentials were made concomitantly with measurement of steroid output.2. Adrenocorticotrophic hormone (ACTH), 10 m-u./ml., induced a sevenfold increase in corticosteroid production rate in normal Krebs solution.3. The steroidogenic response to ACTH was not impaired after omission of [K](o) for 1 hr but was inhibited following exposure to K(+)-free medium for 3 hr. Increase of [K](o) tenfold to 47 mM increased the basal but not the ACTH-stimulated output of corticosteroid whereas raising [K](o) twentyfold to 94 mM enhanced both the basal and ACTH-stimulated steroid production rate. In K(+)-free solution the adrenocortical cells hyperpolarized from - 67 to - 86 mV; subsequently on addition of ACTH they depolarized. Reintroduction of K(+) restored the membrane potential.4. Omission of Ca(2+) partially depolarized the cells but only affected the steroidogenic response to ACTH in the presence of EDTA. A threefold increase of [Ca](o), to 7.68 mM, had no effect on either membrane potentials or steroid formation, but increasing [Ca](o) tenfold to 25.6 mM partially blocked ACTH action. Increasing [Mg](o) twentyfold to 22.6 mM had little effect on ACTH-stimulated corticosteroid output and Sr 2.56 mM, in substitution for Ca(2+), supported ACTH action, but La, 0.25 mM, completely blocked the steroidogenic effect of ACTH.5. Replacement of NaCl, 118 mM by choline chloride, 118 mM, was without effect on ACTH-induced steroidogenesis, whereas LiCl, 118 mM, reduced it by 50%. NaF, 1 and 10 mM, inhibited ACTH-induced steroidogenesis by approximately 60%.6. Nupercaine, 10(-4)M, inhibited the steroid response to ACTH with no effect upon membrane potentials: increasing the nupercaine concentration to 10(-3)M inhibited the steroid response and depolarized the cells. Ouabain, 10(-5)M, induced complete depolarization and suppression of the steroidogenic response to ACTH.7. Action-potential-like changes in membrane potential appeared in cells exposed to ACTH in a K(+)-free medium. The amplitude of the action potentials ranged from 10 to 60 mV according to cell, with a frequency up to 36/min; the frequency tended to increase with time. Tetrodotoxin, 10(-6) g/ml., did not inhibit ACTH-induced action potentials in K(+)-free medium.8. These observations are discussed in relation to the ionic requirements for the steroidogenic action of ACTH. The results further emphasize the dissociation of membrane polarization and the secretion of steroid. The mechanism of output of steroid hormone from the adrenocortical cell may thus differ fundamentally from the secretory mechanisms in other, particle-storing cells.

Action Potentials↗
PubMed1973

Pancreatic acinar cells: acetylcholine-induced membrane depolarization, calcium efflux and amylase release.

1. The effects of acetylcholine upon the output of amylase, Ca(2+) efflux and membrane potential of pancreatic acinar cells have been measured in segments of mouse pancreas superfused in vitro.2. Amylase output was measured continuously using an on-line automated fluorimetric method; Ca(2+) efflux was monitored by measuring the release of (45)Ca(2+) from pre-labelled tissue; and intracellular recordings of acinar transmembrane potentials were obtained with glass micro-electrodes. In some experiments membrane potentials, and in others (45)Ca(2+) efflux, were measured concomitantly with amylase release.3. Acetylcholine depolarized the acinar cells, increased tissue (45)Ca(2+) efflux and raised amylase output, each with a similar dose-dependence, i.e. a maximal response at 10(-5)M, threshold =/< 10(-8)M, and ED(50) values of 0.7 x 10(-7)M, 0.5 x 10(-7)M, and 2 x 10(-7)M for depolarization, amylase release, and (45)Ca(2+) efflux, respectively.4. In response to acetylcholine both depolarization and (45)Ca(2+) efflux preceded or coincided with the increase in amylase output.5. Acetylcholine 10(-5)M and [K](0) 47 mM were without effect on (45)Ca(2+) efflux in the presence of atropine (3 x 10(-6)M) but pancreozymin (0.3 u./ml.) still elicited a marked increase in (45)Ca(2+) release.6. These results suggest that the stimulatory action of acetylcholine on the pancreatic acinar cell involves, sequentially, a specific receptor-activated increase in membrane permeability, depolarization, Ca(2+) mobilization and amylase release. These events are discussed in relation to the integrated mechanism of stimulus-secretion coupling.

Acetylcholine↗
PubMed1972

The ionogenic nature of the secretory-granule membrane. Electrokinetic properties of isolated chromaffin granules.

1. Chromaffin granules isolated from the bovine adrenal medulla possess an electrophoretic mobility of -1.12mum.s(-1).cm.V(-1), corresponding to a surface zeta potential of -14.4mV and surface charge density of 1.38x10(-6)C.cm(-2). 2. The mobility of chromaffin granules is pH-dependent, indicating an amphoteric surface with an isoelectric point at pH3.0 and acidic groups with a pK(a) of 3.11. 3. Addition of bi- and ter-valent cations decreased the mobility of chromaffin granules in a dose-dependent fashion with a relative potency of La(3+)>>Mn(2+)>Ca(2+) >Sr(2+)>Mg(2+)>Ba(2+). 4. Treatment with neuraminidase decreased the mobility of erythrocytes by 84%, whereas chromaffin-granule mobility was decreased by only 14%. This correlates well with the small complement of neuraminic acid present in the granule membrane. 5. The nature, origin and significance of the anionic surface charge of the chromaffin granule is discussed. It is concluded that the net negative charge at the surface of shear derives chiefly from a single type of chemical group, namely -CO(2) (-), contributed by the alpha-carboxyl group of constituent proteins, the phospholipid phosphatidylserine and, to a lesser extent, the sialic acid component of glycoproteins.

Adrenal Medulla↗