PubMed Health⌕ Search

Biomedical subjects

C M Dawson

Publications and source records attributed to C M Dawson.

26 records · Page 2Linked to original sources
PubMed1983

Valinomycin inhibition of the electrical activity of mouse pancreatic beta-cells.

The effect of the K-ionophore valinomycin (VAL) on the electrical activity of single mouse pancreatic beta-cells was measured using the glass micro-electrode technique. In the presence of 11.1 mM glucose, after 4 min of exposure to 10 nM VAL the spike activity was abolished, bursts became irregular and after 10 min the membrane hyperpolarized 4 mV. The electrical activity was completely blocked by 100 nM VAL within 3 min and the membrane hyperpolarization averaged 10 mV. The effect of VAL was irreversible. VAL (100 nM) also inhibited the electrical activity induced by 11.1 mM glucose plus 10 mM tetraethylammonium chloride (TEA), a specific blocker of the voltage sensitive PK. Total inhibition was observed 6-7 min after VAL addition and the cell hyperpolarized 14 mV. With the simultaneous application of 10 mM TEA and 100 microM quinine, a specific blocker of the [Ca2+]i-dependent PK, in the presence of 16.7 mM glucose, the membrane showed continuous activity and progressive depolarization from -45 to -5 mV within 23 min. The subsequent addition of 100 nM VAL also hyperpolarized the cell, with the membrane potential reaching -17 mV after 7 min. On the basis of these data, we suggest that VAL affects the glucose-dependent depolarization of the beta-cell membrane by increasing K+ permeability.

Animals↗
PubMed1982

Potassium-induced insulin release and voltage noise measurements in single mouse islets of Langerhans.

Insulin release and membrane potential fluctuations in response to increased extracellular potassium [K+]o have been measured in single perifused islets of Langerhans from normal mice. An increase in [K+]o from 5 mM to 50 mM induced a transient insulin release with a peak at about 1 min. The peak value was [K+]o-dependent but the half-time t1/2 for the decline was constant at nearly 1 min. 2.5 mM cobalt completely inhibited the potassium-induced stimulation of insulin release. The insulin release elicited by 28 and 50 mM [K+]o was similar in terms of peak, total release and half-time from maximum release. Stepwise increase in [K+]o from 10 to 28 to 50 mM resulted in a normal response to 28 mM but no peak of release after the 28 to 50 mM increase. The results indicate good correlation between excess voltage noise, thought to reflect calcium channel activity, and insulin release evoked by changing extracellular potassium.

Animals↗
PubMed1981

Voltage noise measurements across the pancreatic beta-cell membrane: calcium channel characteristics.

1. Membrane potential fluctuations were measured in cells from mouse Islets of Langerhans identified as beta-cells by the characteristic pattern of electrical activity induced by 11 mM-D-glucose. 2. The membrane potential was controlled by adjusting the external potassium concentration, [K+]o, keeping the sum [Na+]o plus [K+]o constant. In the absence of glucose, when [K+]o is raised, the resulting depolarization is accompanied by a significant increase in voltage noise. 3 The amplitude and time course of the voltage noise were measured under various experimental conditions. The variance of the fluctuating voltage decreased monotonically along the depolarization induced by sudden increase in [K+]o, suggesting a monotonic reduction in the number of elementary events. 4. The frequency characteristics of the excess noise could be analysed as the sum of 1/f and 1/f2 components. While the 1/f component remained unaffected by the external application of 20mM-tetraethylammonium (TEA) and either 2 mM-Mn2+ or 2 mM-Co2+, the 1/f2 component was suppressed by both Mn2+ and Co2+. 5. The corner frequency, fc, of the 1/f2 component depended on membrane potential, which was adjusted by adjusting the [K+]o jump. These results support the idea that fc in these experiments is a measure of the channel relaxation. 6. Measurements of the input resistance in the frequency range from 0 to 25 Hz were used to obtain a rough estimate of the size of the channel conductance as 5 x 10(-12) omega (-1).

Animals↗
PubMed1980

The nature of the oscillatory behaviour in electrical activity from pancreatic beta-cell.

The typical burst pattern of electrical activity recorded from beta-cells of mouse islets in the presence of 11.1 mM glucose has been compared from 225 cells in terms of two parameters: relative duration of the active phase and periodicity of the oscillations between active and silent phases. The two parameters show different distributions, Gaussian and bimodal respectively. Burst periodicity was found to increase dramatically at external potassium concentrations below 2mM, while the relative duration of the active phase was little affected at concentrations as low as 0.5 mM. Increasing external calcium concentration significantly increased the amplitude of the bursts but greatly decreased the relative duration of the active phase. Quinine, in the absence of glucose, induced depolarization and electrical activity and stimulated insulin release from perifused mouse islets; spike frequency and insulin release followed a monophasic pattern. A model has been proposed for the beta-cell explaining the experimental results in terms of a feedback mechanism between calcium permeability activated by depolarization of the cell membrane and potassium permeability activated by an increase in the concentration of intracellular ionized calcium [Ca2+]i. The results are in agreement with the hypothesis that a [Ca2+]i-dependent potassium permeability, specifically blocked by quinine, controls membrane potential and insulin release.

Action Potentials↗
PubMed1979

Potassium permeability activated by intracellular calcium ion concentration in the pancreatic beta-cell.

1. Membrane potentials and input resistance were measured in beta-cells from mouse pancreatic islets of Langerhans in a study designed to assess the role of a K permeability specifically blocked by quinine or quinidine and activated by intracellular calcium ion concentration ([Ca2+])i-activated PK). 2. Addition of 100 microM-quinine to the perifusion medium resulted in a 10--30 mV depolarization of the membrane and an increase in the input resistance of ca. 4.10(7) omega. 3. In the absence of glucose, 100 microM-quinine induced electrical activity. 4. In the presence of glucose, 100 microM-quinine abolished the burst pattern of electrical activity and very much reduced the graded response of spike frequency normally seen with different concentrations of glucose. 5. Addition of mitochondrial inhibitors, KCN, NaN3, DNP, CCCP, FCCP, to the perifusion medium containing glucose rapidly hyperpolarized the beta-cell membrane, inducing a concomitant decrease in input resistance. 6. In the presence of glucose, these mitochondrial inhibitors reversibly blocked electrical activity; upon removal of the inhibitor, recovery of electrical activity followed a biphasic pattern. 7. The effects of mitochondrial inhibitors were partially reversed by 100 microM-quinine. 8. It is proposed that the membrane potential of the beta-cell in the absence of glucose is predominantly controlled by the [Ca2+]i-activated PK. It is further suggested that this permeability to K controls the level for glucose stimulation and leads to the generation of the burst pattern.

Action Potentials↗