Up-regulation of pressure-activated Ca(2+)-permeable cation channel in intact vascular endothelium of hypertensive rats.

In endothelial cells, stretch-activated cation channels have been proposed to act as mechanosensors for changes in hemodynamic forces. We have identified a novel mechanosensitive pressure-activated channel in intact endothelium from rat aorta and mesenteric artery. The 18-pS cation channel responded with a multifold increase in channel activity when positive pressure was applied to the luminal cell surface with the patch pipette and inactivated at negative pipette pressure. Channel permeability ratio for K+, Na+, and Ca2+ ions was 1:0.98:0.23. Ca2+ influx through the channel was sufficient to activate a neighboring Ca2(+)-dependent K+ channel. Hemodynamic forces are chronically disturbed in arterial hypertension. Endothelial cell dysfunction has been implicated in the pathogenesis of arterial hypertension. In two comparative studies, density of the pressure-activated channel was found to be significantly higher in spontaneously hypertensive rats and renovascular hypertensive rats compared with their respective normotensive controls. Channel activity presumably leads to mechanosensitive Ca2+ influx and induces cell hyperpolarization by K+ channel activity. Both Ca2+ influx and hyperpolarization are known to induce a vasodilatory endothelial response by stimulating endothelial nitric oxide (NO) production. Up-regulation of channel density in hypertension could, therefore, represent a counterregulatory mechanism of vascular endothelium.

Molecular cloning and functional characterization of the Xenopus Ca(2+)-binding protein frequenin.

Frequenin was originally identified in Drosophila melanogaster as a Ca(2+)-binding protein facilitating transmitter release at the neuromuscular junction. We have cloned the Xenopus frequenin (Xfreq) by PCR using degenerate primers combined with low-stringency hybridization. The deduced protein has 70% identity with Drosophila frequenin and about 38-58% identity with other Ca(2+)-binding proteins. The most prominent features are the four EF-hands, Ca(2+)-binding motifs. Xfreq mRNA is abundant in the brain and virtually nondetectable from adult muscle. Western blot analysis indicated that Xfreq is highly concentrated in the adult brain and is absent from nonneural tissues such as heart and kidney. During development, the expression of the protein correlated well with the maturation of neuromuscular synapses. To determine the function of Xfreq at the developing neuromuscular junction, the recombinant protein was introduced into Xenopus embryonic spinal neurons by early blastomere injection. Synapses made by spinal neurons containing exogenous Xfreq exhibited a much higher synaptic efficacy. These results provide direct evidence that frequenin enhances transmitter release at the vertebrate neuromuscular synapse and suggest its potential role in synaptic development and plasticity.

XI. Catalogue of Harvard graduates, [ca. 1810]

This paper notebook contains a handwritten, alphabetical listing of graduates of the Harvard Classes of 1642 to 1809 presumably compiled from the published Triennial Catalogues.

Eulogy of George Washington, ca. 1800

This manuscript, which White entitled A faint sketch of the character, history & services of the Immortal Washington, appears to be a draft of the eulogy on Washington that he delivered publicly in Methuen and which was printed by Seth H. Moore and published by in February 1800.

Outlines of Holden Chapel, [ca. 1801]

Pen and ink drawings with measurements of the interior ground plot, arch, and side of Holden Chapel.

Sundry extracts on the subject of the taxation of College &c., ca. 1798-1801

Notebook with brown paper cover containing handwritten extracts from the charters and related legislation of New England academic, charitable, and commercial institutions regarding their ability to hold real estate and related tax exemptions. Most of the listed documents are dated in the 1780s and 1790s. The notebook also contains extracts from "Argument in the case of Poor's rate, charged on the College of Christ & Emmanuel in the University of Cambridge 1768." The item title is transcribed from a handwritten inscription on the back cover.