Involvement of K channels and calcium-independent mechanisms in hydrogen sulfide-induced relaxation of rat mesenteric small arteries.

Endogenous hydrogen sulfide (H2S) is involved in the regulation of vascular tone. We hypothesized that lowering of calcium and opening of K channels as well as calcium-independent mechanisms are involved in H2S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H2S] after addition to closed tubes of NaSH, Na2S, and GYY4137 were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H2S], GYY4137 caused more relaxation in relation to released free [H2S] than NaSH and Na2S in rat mesenteric small arteries. Simultaneous measurements of [H2S] and tension showed that 15 μM of free H2S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaSH lowered calcium and caused relaxation of norepinephrine-contracted arteries, while high extracellular potassium reduced NaSH relaxation without corresponding calcium changes. In norepinephrine-contracted arteries, NaSH (1 mM) lowered phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) remained unchanged. Inhibitors of guanylate cyclase, protein kinase A and G failed to reduce NaSH relaxation, while blockers of voltage-gated KV7 channels inhibited NaSH relaxation, and blockers of mitochondrial complex I and III abolished NaSH relaxation. CONCLUSION: the present findings suggest that low micromolar concentrations of free H2S by a dual mechanism opens K channels followed by lowering of smooth muscle calcium and by a mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation

A community-based transcriptomics classification and nomenclature of neocortical cell types

To understand the function of cortical circuits it is necessary to classify their underlying cellular diversity. Traditional attempts based on comparing anatomical or physiological features of neurons and glia, while productive, have not resulted in a unified taxonomy of neural cell types. The recent development of single-cell transcriptomics has enabled, for the first time, systematic high-throughput profiling of large numbers of cortical cells and the generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data have revealed the existence of clear clusters, many of which correspond to cell types defined by traditional criteria, and which are conserved across cortical areas and species. To capitalize on these innovations and advance the field, we, the Copenhagen Convention Group, propose the community adopts a transcriptome-based taxonomy of the cell types in the adult mammalian neocortex. This core classification should be ontological, hierarchical and use a standardized nomenclature. It should be configured to flexibly incorporate new data from multiple approaches, developmental stages and a growing number of species, enabling improvement and revision of the classification. This community-based strategy could serve as a common foundation for future detailed analysis and reverse engineering of cortical circuits and serve as an example for cell type classification in other parts of the nervous system and other organs