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Osteoclasts are the cells responsible for the resorption of bone and other mineralized tissues. GTP-binding proteins (G proteins) play important roles in regulating the activity of many cell types; however, there is limited knowledge of their functions in osteoclasts. We used the patch-clamp technique in the whole-cell configuration to introduce either hydrolysis-resistant guanosine triphosphate analogues or fluoroaluminate into single rat osteoclasts, and examined the effects of G protein activation on cell morphology and ionic conductances. Guanosine 5'-O-(3-thiotriphosphate) or 5'-guanylyl-imidodiphosphate, but not the control compounds adenosine 5'-O-(3-thiotriphosphate) or guanosine 5'-O-(2-thiodiphosphate), induced: (1) prompt spreading due to extension of lamellipodia; and (2) after a latency of several minutes, complete suppression of the inwardly rectifying K+ current. Pertussis toxin did not alter either spreading or suppression of K+ current induced by guanosine 5'-O-(3-thiotriphosphate). Cytochalasin D, but not colchicine, prevented guanosine 5'-O-(3-thiotriphosphate)-induced spreading, consistent with actin polymerization underlying lamellipod extension. Whole-cell capacitance did not change during guanosine 5'-O-(3-thiotriphosphate)-induced spreading, which is consistent with a lack of change in total plasma membrane area. Fluoroaluminate did not induce spreading, but it did suppress the K+ current. The differential effects of fluoroaluminate and guanosine 5'-O-(3-thiotriphosphate) suggest that lamellipod extension is regulated by a small molecular mass, monomeric G protein, whereas the inwardly rectifying K+ current is regulated by a large molecular mass, heterotrimeric G protein. Thus, osteoclast motility and ion transport are regulated by separate G protein-coupled pathways.

Hydrogen peroxide (H2O2) produces complex cardiac effects that may involve altered calcium homeostasis. The cardiotoxic effects of H2O2 can be attenuated by adenosine A1 receptor agonists. The present study examined the effect of H2O2 on L-type Ca++ current (ICa,L) in guinea pig ventricular myocytes under two different recording conditions and the influence of adenosine receptor agonists. H2O2 (100 microM), did not have any significant effect on ICa,L, under conventional whole cell patch configuration. However, when recorded under nystatin perforated patch configuration, H2O2 caused a gradual and significant increase (84 +/- 14%) in ICa,L compared to control values. N6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, significantly attenuated the effect of H2O2. The inhibitory effect of N6-cyclopentyladenosine was antagonized by 8cyclopentyl-1, 3-dipropylxanthine, an adenosine A1 receptor antagonist. The A2A and A3 receptor agonists, 2-p-(2-Carboxyethyl)phenethylamino-5'- N - ethylcarboxamidoadenosine (CGS-21680) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide, respectively, did not modulate the enhancement of ICa,L by H2O2. Moreover the effects of N6-cyclopentyladenosine were mimicked by the protein kinase C inhibitor bisindolylmaleimide. Thus, our results demonstrate a potent stimulatory effect of H2O2 on ICa,L in guinea pig ventricular myocytes. We further demonstrate that adenosine A1 receptor activation attenuates this effect. Our results suggest a potential basis for altered calcium homeostasis in response to H2O2 as well as the salutary effects of A1 receptor activation against H2O2-induced cardiotoxicity.

The effect of substance P on freshly dissociated gastric smooth muscle cells was examined electrophysiologically. Substance P caused depolarization, associated with a membrane conductance decrease, which led to the generation of action potentials and contraction. When the membrane potential was held constant under voltage clamp, substance P induced a net inward current, also associated with a conductance decrease. The net inward current resulted from suppression of an outward K+ current, one which resembled the acetylcholine-sensitive M-current in these cells. When substance P maximally suppressed this outward K+ current, acetylcholine (ACh) had no additional effect. Conversely, when ACh fully suppressed the M-current, substance P was without additional effect. These results indicate that substance P suppresses the same outward K+ current affected by ACh. Suppression of M-current by substance P was observed in approximately half (44 of 85) of the cells studied in these experiments. In those cells that did not respond to substance P, ACh was nevertheless capable of suppressing the M-current. Thus both substance P and cholinergic agonists appear to exert their excitatory effects on smooth muscle cells by inhibiting a common K+ current.

We have studied some passive electrical properties of uterine smooth muscle to determine whether a change in electrical parameters accompanies gap junction formation at delivery. The length constant of the longitudinal myometrium increased from 2.6 +/- 0.8 mm (X +/- SD) before term to 3.7 +/- 1 mm in tissues from delivering animals. The basis of the change was a 33% decrease in internal resistance and a 46% increase in membrane resistance. Axial current flow in an electrical syncytium such as myometrium is impeded by the cytoplasm of individual cells plus the junctions between cells. Measurement of the longitudinal impedance indicated that the specific resistance of the myoplasmic component was constant at 319 +/- 113 omega . cm before term and 340 +/- 93 omega . cm at delivery. However, a decrease in junctional resistance was apparent from 323 +/- 161 omega . cm to 134 +/- 64 omega . cm at delivery. 1.5-2 d after delivery, the junctional resistance was increased, as was the myoplasmic resistance. Thin-section electron microscopy of some of the same muscle samples showed that gap junctions were present in significantly greater numbers in the delivering tissues. Therefore, our results support the hypothesis that gap junction formation at delivery is associated with improved electrical coupling of uterine smooth muscle.

Membrane properties of freshly isolated rat osteoclasts were studied using the whole cell patch-clamp recording technique. The membrane potential could switch between two stable levels, approximately -70 and -15 mV. Voltage-clamp studies indicated that osteoclasts exhibited marked inward rectification, with hyperpolarizing voltage commands from -70 mV activating large inward currents. No voltage-dependent currents were observed in response to depolarization. An increase in external K+ concentration shifted the current-voltage relationship positive in a manner predicted for K+ current. Furthermore, barium and cesium reversibly suppressed the inward current. Thus the dominant current evident in osteoclasts was inwardly rectifying K+ current, resembling that found in a number of cell types, including cardiac and skeletal muscle and oocytes. The current-voltage relationship of osteoclasts was "N-shaped" and could intersect the zero-current level at three potentials, accounting for two stable membrane potentials. Switching of membrane potential between these two levels may regulate a number of the cellular processes involved in bone resorption.

In this review, we describe four approaches to the materials synthesis of organized inorganic matter. These include the use of self-assembled organic templates (transcriptive synthesis), cooperative assemblies of templates and building blocks (synergistic synthesis), spatially restricted reaction fields (morphosynthesis), and combinations of these approaches (integrative synthesis) in the area of sol−gel chemistry. We illustrate these strategies, respectively, by describing recent work on the formation of silica-based organized materials, viz. the preparation of ordered silica macrostructures using bacterial templates, template-directed synthesis of ordered hybrid mesophases and organoclays, synthesis of microskeletal frameworks of silica and other metal oxides in compartmentalized liquids, and use of bacterial superstructures in the fabrication of hierarchical macrostructures of mesoscopically ordered silica.

The kinetics of a Q-switched laser is discussed in a qualitative fashion. It is shown that the occurrence of multiple pulses can be prevented by the use of a sufficiently fast switch. A Lummer-Gehrcke plate used in a novel fashion in conjunction with a rotating prism is shown to be a “fast” switch. Experimental results are presented which show substantial improvement over previous Q-switching schemes.

Measurements were made of the thermally induced distortions occurring in laser rods as a result of flash lamp heating. Time-resolved interferograms were obtained by placing the sample in a Mach–Zehnder interferometer and utilizing a Q-switched laser as the interferometer-illumination source. It was observed that significant distortions occur during the pumping pulse leading to diverging-lens effects in the sample rods.

A calorimeter for measuring the output energy of optical masers has been made. It consists essentially of several thermistor beads connected in a bridge circuit and placed in intimate contact with a carbon cone into which the maser beam is directed. The instrument is wide band and easily calibrated. A description of the calorimeter and some results of energy measurements of a ruby optical maser are presented in this paper.

Presents several letters to the editor. Views of the U.S. Navy Admiral on German submarines; Performance of the play "Anna Christie," in Soviet Union; Description of works of Spanish playwright Jacinto Benavente.

The alcohol dehydrogenase locus (adh) is polymorphic in most natural populations of Drosophila melanogaster1–11. Eight alleles have been identified on the basis of allozyme elec-trophoretic mobility and thermostability; two of these, adhFmand adhSm, generally have combined frequencies of ⩾90%. In four widely separate locations these major alleles display a clinal change in frequency, that of adh Fmincreasing with latitude and altitude3–6,11. Biochemical studies have shown that the Fm allozyme (ADHFm) is more active, but less heat-resistant, than ADHSm(refs 12–14). The fact that these differences are associated with the geographical distribution of the alleles suggests that environmental temperature may be a selective factor in maintaining this polymorphism. We have investigated the effect of high temperature on flies having ADH allozymes with a range of thermostabilities and report here that flies which have relatively labile enzymes show reduced survival on alcohol-supplemented food compared with flies possessing more heat-resistant allozymes.