Concentration clamping

L. L. Gustafsson, W. F. Ebhng, E. Osaki, S. Harapat, D. R. Stanski, and S. L. Shafer, Plasma concentration clamping in the rat nsing a compnter-controUed infnsion pnmp. Pharm Res 9 800-807 (1992). 

Water Transport. Two methods of measuring water-vapor transmission rates (WVTR) ate commonly used. The newer method uses a Permatran-W (Modem Controls, Inc.). In this method a film sample is clamped over a saturated salt solution, which generates the desired humidity. Dry air sweeps past the other side of the film and past an infrared detector, which measures the water concentration in the gas. For a caUbrated flow rate of air, the rate of water addition can be calculated from the observed concentration in the sweep gas. From the steady-state rate, the WVTR can be calculated. In principle, the diffusion coefficient could be deterrnined by the method outlined in the previous section. However, only the steady-state region of the response is serviceable. Many different salt solutions can be used to make measurements at selected humidity differences however, in practice,... 

The metal film is then electroplated with copper, and the metal part brazed to the copper plating. Adhesives, usually epoxy resins, are used to join parts at low temperatures. Finally, ceramic parts can be clamped together, provided the clamps avoid stress concentrations, and are provided with soft (e.g. rubber) packing to avoid contact stresses. 

B. Putrescine dihydrochloride. A 2-1. wide-mouthed Erlen-meyer flask containing 200 ml. of concentrated hydrochloric acid and 400 g. of cracked ice is clamped in an ice-salt bath and provided with an efficient stirrer (inefficient stirring may lower the yield). The stirring is started, and 80 g. (0.46 mole) of adipyl hydrazide is added all at once, followed by 500 ml. of ether (Note 5). While the temperature is maintained below 10° (Note 6), a solution of 80 g. (1.15 moles) of sodium nitrite in 150 ml. of water is added over about 30 minutes through a dropping funnel whose stem reaches below the bottom of the ether layer, but not into the path of the stirrer. The operations in the next paragraph should be conducted without delay after the completion of the addition of the nitrite. 

On the basis of the principle of grafted TLC, reversed-phase (RP) and normal-phase (NP) stationary phases can also be coupled. The sample to be separated must be applied to the first (2.5 cm X 20 cm) reversed-phase plate (Figure 8.16(a)). After development with the appropriate (5ti 5yi) mobile phase (Figure 8.16(b)), the first plate must be dried. The second (20 cm X 20 cm) (silica gel) plate (Figure 8.16(c)) must be clamped to the first (reversed-phase) plate in such a way that by use of a strong solvent system (Sj/, SyJ the separated compounds can be transferred to the second plate (Figure 8.16(d)). Figure 8.16(e) illustrates the applied, re-concentrated... 

Concentrated at free end Cantilever, 1 free, 1 clamped Free end 1/3 1... 

In a different context, a micropipette has been applied to monitor the current through a single-ion channel in a biological membrane. The patch-clamp technique invented by Sackmann and Neher [119] led to their Nobel Prize in medicine. The variations in channel current with voltage, concentration, type of ions, and type of channels have been explored. While the functions of specific channels, in particular their ionic selectivity, have been well known, only a handful of channels have the internal geometry and charge distribution determined. The development of a theory to interpret the mass of channel data and to predict channel action is still lacking. 

Using the cell-attached patch clamp technique on frog muscle fibers (79), one can observe only two conditions the open, conducting state of the receptor and a nonconducting state of unknown identity. The transitions behave according to stochastic principles the lifetimes of any particular condition are distributed exponentially. The open state has a mean duration that is the inverse of the rate of channel closing. Because channel open time depends only upon a conformational shift, agonist concentration does not influence the parameter. It is, however, influenced... 

The primary characteristic of a sequential blocker, as observed with the patch clamp technique, is that the reciprocal of the mean duration of the lifetime equals the normal channel closing rate plus the rate constant of channel blockade times the drug concentration. Therefore, increasing the drug concentration shortens the mean channel open time. 

These approaches to receptor identification and classification were, of course, pioneered by studies with peripheral systems and isolated tissues. They are more difficult to apply to the CNS, especially in in vivo experiments, where responses depend on a complex set of interacting systems and the actual drug concentration at the receptors of interest is rarely known. However, the development of in vitro preparations (acute brain slices, organotypic brain slice cultures, tissue-cultured neurons and acutely dissociated neuronal and glial cell preparations) has allowed more quantitative pharmacological techniques to be applied to the action of drugs at neurotransmitter receptors while the development of new recording methods such as patch-clamp... 

---