Stretch-activated single K+ channels account for whole-cell currents elicited by swelling

Functionally significant stretch-activated ion channels have been clearly identified in excitable cells. Although single-channel studies suggest their expression in other cell types, their activity in the whole-cell configuration has not been shown. This discrepancy makes their physiological significance doubtful and suggests that their mechanical activation is artifactual. Possible roles for these molecules in nonexcitable cells are acute cell-volume regulation and, in epithelial cells, the complex adjustment of ion fluxes across individual cell membranes when the rate of transepithelial transport changes. We report the results of experiments on isolated epithelial cells expressing in the basolateral membrane stretch-activated K+ channels demonstrable by the cell-attached patch-clamp technique. In these cells, reversible whole-cell currents were elicited by both isosmotic and hyposmotic cell swelling. Cation selectivity and block by inorganic agents were the same for single-channel and whole-cell currents, indicating that the same entity underlies single-channel and whole-cell currents and that the single-channel events are not artifactual. In these cells, when the rate of apical-membrane NaCl entry increases, the cell Na+ content and volume also increase, stimulating the Na+,K+-ATPase at the basolateral membrane, i.e., both Na+ extrusion and K+ uptake increase. We speculate that, under these conditions, the parallel activation of basolateral K+ channels (by the swelling) elevates conductive K+ loss, tending to maintain the cell K+ content constant (“pump-leak parallelism”). This study describes a physiologically relevant stretch-activated channel, at both the single-channel and whole-cell levels, in a nonneural cell type.

Online tables of contents for books: effect on usage*

Objectives: To explore whether the presence of online tables of contents (TOC) in an online catalog affects circulation (checkouts and inhouse usage). Two major questions were posed: (1) did the presence of online tables of contents for books increase use, and, (2) if it did, what factors might cause the increase?

Brandon/Hill selected list of print books and journals for the small medical library*

After thirty-six years of biennial updates, the authors take great pride in being able to publish the nineteenth version (2001) of the “Brandon/Hill Selected List of Print Books and Journals for the Small Medical Library.” This list of 630 books and 143 journals is intended as a selection guide for health sciences libraries or similar facilities. It can also function as a core collection for a library consortium. Books and journals are categorized by subject; the book list is followed by an author/editor index, and the subject list of journals, by an alphabetical title listing. Due to continuing requests from librarians, a “minimal core list” consisting of 81 titles has been pulled out from the 217 asterisked (*) initial-purchase books and marked with daggers (†*) before the asterisks. To purchase the entire collection of 630 books and to pay for 143 2001 journal subscriptions would require $124,000. The cost of only the asterisked items, books and journals, totals $55,000. The “minimal core list” book collection costs approximately $14,300.

Brandon/Hill selected list of print books and journals in allied health*

This list of 424 books and 77 journals is intended as a selection guide for print literature to be used in a library supporting allied health educational programs or allied health personnel in either an academic or health care setting. Because of the impossibility of covering the large number and wide variety of allied health professions and occupations, the recommended publications are focused primarily on the educational programs listed and recognized by the American Medical Association and other accrediting bodies. Books and journals are categorized by subject; the book list is followed by an author/editor index, and the subject list of journals by an alphabetical title listing. Items suggested for initial purchase (167 books and 31 journals) are indicated by asterisks. To purchase the entire collection of books and journals (2000 subscriptions) would require an expenditure of about $31,970. The cost of only the asterisked items totals $12,515.

Decreased food intake does not completely account for adiposity reduction after ob protein infusion.

The effects of recombinantly produced ob protein were compared to those of food restriction in normal lean and genetically obese mice. Ob protein infusion into ob/ob mice resulted in large decreases in body and fat-depot weight and food intake that persisted throughout the study. Smaller decreases in body and fat-depot weights were observed in vehicle-treated ob/ob mice that were fed the same amount of food as that consumed by ob protein-treated ob/ob mice (pair feeding). In lean mice, ob protein infusion significantly decreased body and fat-depot weights, while decreasing food intake to a much lesser extent than in ob/ob mice. Pair feeding of lean vehicle-treated mice to the intake of ob protein-treated mice did not reduce body fat-depot weights. The potent weight-, adipose-, and appetite-reducing effects exerted by the ob protein in ob protein-deficient mice (ob/ob) confirm hypotheses generated from early parabiotic studies that suggested the existence of a circulating satiety factor of adipose origin. Pair-feeding studies provide compelling evidence that the ob protein exerts adipose-reducing effects in excess of those induced by reductions in food intake.

Brain localization for arbitrary stimulus categories: a simple account based on Hebbian learning.

A central theme of cognitive neuroscience is that different parts of the brain perform different functions. Recent evidence from neuropsychology suggests that even the processing of arbitrary stimulus categories that are defined solely by cultural conventions (e.g., letters versus digits) can become spatially segregated in the cerebral cortex. How could the processing of stimulus categories that are not innate and that have no inherent structural differences become segregated? We propose that the temporal clustering of stimuli from a given category interacts with Hebbian learning to lead to functional localization. Neural network simulations bear out this hypothesis.

G protein activation kinetics and spillover of gamma-aminobutyric acid may account for differences between inhibitory responses in the hippocampus and thalamus.

We have developed a model of gamma-aminobutyric acid (GABA)ergic synaptic transmission mediated by GABAA and GABAB receptors, including cooperativity in the guanine nucleotide binding protein (G protein) cascade mediating the activation of K+ channels by GABAB receptors. If the binding of several G proteins is needed to activate the K+ channels, then only a prolonged activation of GABAB receptors evoked detectable currents. This could occur if strong stimuli evoked release in adjacent terminals and the spillover resulted in prolonged activation of the receptors, leading to inhibitory responses similar to those observed in hippocampal slices. The same model also reproduced thalamic GABAB responses to high-frequency bursts of stimuli. In this case, prolonged activation of the receptors was due to high-frequency release conditions. This model provides insights into the function of GABAB receptors in normal and epileptic discharges.