The properties of a system consisting of a thin phospholipid film separating two electrolyte solutions containing 1MM 2,4-dinitrophenol have been studied. Both the variation of electrical conductance as a function of pH, keeping the pH the same on both sides of the membrane, and the nonlinear variation of electrical potential difference as a function of pH difference across the membrane have been explained in terms of lipid-soluble complexes of the typeXP 2 (-) whereX is a cation andP dinitrophenate. The maximum conductance was found to be 1.4×10(-5) mhos cm(-2) at pH 4.2.

SUMMARYThe effects of glibenclamide on the electrical activity of the fl-cells of the islets of Langerhans of normal mice have been investigated in the absence and presence of glucose (11 1 mM). Glibenclamide depolarized the cell membrane and this has been interpreted in terms of an increase in the ratio of the Na+ and K+ permeabilities, PNa/PK. This ratio increased from 0 05 to 0 24 in the presence of 4 /tM glibenclamide and zero glucose. The input resistance of the fl-cells also increased. These observations indicate a decrease in K+ permeability. The effect is only slowly reversed after removal of glibenclamide. Uncouplers of oxidative phosphorylation do not reverse the depolarization induced by glibenclamide. It is suggested that glibenclamide is acting directly to inhibit the [Ca2+]i-gated K+ permeability in the fl-cell membrane.

Measurements of *°Rb" efllux from perifused collagenase-isolated mouse islets and membrane potential from microdissected mouse islets have been used to estimate, using the Goldman model, the potassium permeability coeflicient (PK) and potassium conductance (gK) of the cell membrane. In the presence of low glucose (2.8 mM) PK=2.5 ><10'9 m sec" and gK=0.22 S m'2 and at high glucose (22.2 mM) PK=0.96 >< l0'9 m sec" and gK=0.13 S m'2. There was a tendency for PK to fall slowly with time. Following return to low glucose, there was a transient decrease in efflux rate constant. However, this is not reflected in the calculated PK. It is clear that flux data for ions, in the absence of membrane potential measurements, should be interpreted with caution.From studies on ob/ob mouse islets, Sehlin and Téiljedal (15) proposed that a decrease in potassium permeability is responsible for the glucose-induced depolarization of pancreatic fi-cells. Subsequently, other workers (3, 4, 10, 11, 14) confirmed, using 4214+ and 36Rb", that an increase in glucose concentration reduced the ion flux in rat islets. It was shown that 8°Rb" was a satisfactory tracer for potassium (4, 10). Measurements of input resistance in mouse islets showed that membrane conductance was decreased by high glucose (1). In order to determine the permeability coefiicient and the conductance of the cell membrane from the efllux rate constant, it is necessary to know the membrane potential and this has not been determined in rat islets.The data presented here, obtained using normal mouse islets, confirm quantitatively the inhibitory effect of high glucose on 86Rb+ efiiux found in rat islets. However, using values of the membrane potential in low and high glucose, the results for mouse islets can be expressed in terms of permeability coefficients and conductances, calculated using the Goldman model. MATERIALS AND METHODSThe solution used was modified Krebs; 120 mM NaCl, 25 mM NaHCO3, 5 mM KCI, 2.56 mM CaCl2 and 1.1 mM MgCl2 equilibrated with 95 'X, O2/5% CO2 at 37°C to maintain the pH at 7.4 and containing either 2.8 or 22.2 mM glucose. For flux experiments, the medium also contained 5 mg cm" bovine serum albumin (Fraction V Armour Pharmaceuticals, Eastbourne, England).Isolated islets were prepared from normal albino mice using collagenase (Sigma, type V). 100-150 islets were incubated at 37°C for 2h in 0.1 cma of medium containing 2.8 mM glucose and 10 ,uCi of 86Rb+ (Amersham International, specific activity 0.3-0.5 mCi/mg). After washing three times at room temperature with 2.5 cm3 of unlabelled medium, the islets were transferred to the perifusion chamber. This was a modified plastic syringe with volume adjusted to 0.2 cm3. The flow rate was 0.5 cm3 min" 1 and the half-time for the perifusion system was 27 sec. The perifusate was collected at 1 min intervals. "Rb" in the samples and the residual remaining in the islets at the end of the experiment was counted using fi-scintillation counting (Picofiuor 15).

The present study was designed to assess the feasibility of using small doses of a stable isotope of Zn to follow plasma kinetics over a 10 d period and, hence, make deductions about Zn turnover and body pool sizes. At the beginning of the 10 d metabolic balance, two adults, consuming their habitual diet, were given an intravenous injection of 70Zn. There was a fourfold difference in the administered dose between the two subjects (0.445 and 2.078 mg). Blood samples were taken at regular intervals and plasma enrichment with 70Zn measured by thermal ionization mass spectrometry. Urine and faeces were collected and analysed for Zn and ' OZn. Kinetic analysis of the plasma 70Zn decay by several different methods was undertaken. It was apparent from both deconvolution analysis of the short-term (0-90 min) decay data and four-compartment modelling of the longer-term (0-24 h) data that isotopic Zn very rapidly equilibrates with the plasma Zn and with a rapidly exchanging non-plasma pool, probably located within the liver. This latter pool appears to contain less than 10mg Zn and the peak of isotope enrichment occurs at about 20 min post injection. The later decay of plasma Zn enrichment appears to be dictated by exchange with a much larger pool of approximate size 350 mg.

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