Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca2+-activated K+ channels (SKCa and IKCa) underpins EDH-mediated responses. It was recently reported that Ca2+ influx through endothelial transient receptor potential vanilloid type 4 ...

NREM sleep is characterized by K-complexes (KCs), over the negative phase of which we identified brief activity in the theta range. We recorded high resolution EEG of whole-night sleep from seven healthy volunteers and visually identified 2nd and 3rd stage NREM spontaneous KCs. We identified three major categories: (1) KCs without intra-KC-activity (iKCa), (2) KCs with non-oscillatory iKCa, and...

Cysteine-scanning mutagenesis (SCAM) and computer-based modeling were used to investigate key structural features of the S6 transmembrane segment of the calcium-activated K(+) channel of intermediate conductance IKCa. Our SCAM results show that the interaction of [2-(trimethylammonium)ethyl] methanethiosulfonate bromide (MTSET) with cysteines engineered at positions 275, 278, and 282 leads to c...

Endothelial cell (EC) Ca-activated K channels (SKCa and IKCa channels) generate hyperpolarization that passes to the adjacent smooth muscle cells causing vasodilation. IKCa channels focused within EC projections toward the smoothmuscle cells are activated by spontaneous Ca events (Ca puffs/pulsars). We now show that transient receptor potential, vanilloid 4 channels (TRPV4 channels) also cluste...

Tao R, Lau CP, Tse HF, Li GR. Regulation of cell proliferation by intermediate-conductance Ca -activated potassium and volumesensitive chloride channels in mouse mesenchymal stem cells. Am J Physiol Cell Physiol 295: C1409–C1416, 2008. First published September 24, 2008; doi:10.1152/ajpcell.00268.2008.—Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for regenerative medici...

Stimulation of vascular calcium-sensing receptors (CaSRs) is reported to induce both constrictions and relaxations. However, cellular mechanisms involved in these responses remain unclear. The present study investigates the effect of stimulating CaSRs on vascular contractility and focuses on the role of the endothelium, nitric oxide (NO) and K(+) channels in these responses. In wire myography s...

The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca(2+)-activated K(+) channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on [Ca(2+)]out. Also it has been suggested that K(+) is important through localized [K(+)]out signaling causing ac...

We present in this work a structural model of the open IKCa (KCa3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. This analysis showed that the selectivity filter and the region extending from the channel inner cavity to the internal medium should respectively account for 81% and ...

Small increases in extracellular Ca dilate isolated blood vessels. In the present study, the possibility that a vascular, extracellular Ca -sensing receptor (CaSR) could mediate these vasodilator actions was investigated. Novel ligands that interact with the CaSR were used in microelectrode recordings from rat isolated mesenteric and porcine coronary arteries. The major findings were that (1) r...

Small increases in extracellular Ca2+ dilate isolated blood vessels. In the present study, the possibility that a vascular, extracellular Ca2+-sensing receptor (CaSR) could mediate these vasodilator actions was investigated. Novel ligands that interact with the CaSR were used in microelectrode recordings from rat isolated mesenteric and porcine coronary arteries. The major findings were that (1...