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The voltage-sensitive sodium channel Na(v)1.5 (encoded by SCN5A) is expressed in electromechanical organs and is mechanosensitive. This study aimed to determine the mechanosensitive transitions of Na(v)1.5 at the molecular level. Na(v)1.5 was expressed in HEK 293 cells and mechanosensitivity was studied in cell-attached patches. Patch pressure up to -50(More)
The gastrointestinal tract serves the physiological function of digesting and absorbing nutrients from food and physically mixing and propelling these contents in an oral to anal direction. These functions require the coordinated interaction of several cell types, including enteric nerves, immune cells and smooth muscle. Interstitial cells of Cajal (ICC)(More)
Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. The aim of this study was to determine expression of a Na+ current in human intestinal ICC and to determine the effects of the Na+ current on the slow wave. Visually(More)
Voltage-gated sodium selective ion channel Na(V)1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. Na(V)1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon Na(V)1.5 to modulate activity by multiple mechanisms. This study examined(More)
BACKGROUND The pathophysiological basis of diabetic gastroparesis is poorly understood, in large part due to the almost complete lack of data on neuropathological and molecular changes in the stomachs of patients. Experimental models indicate various lesions affecting the vagus, muscle, enteric neurons, interstitial cells of Cajal (ICC) or other cellular(More)
Tetrodotoxin-resistant Na+currents are expressed in a variety of muscle cells including human jejunal circular smooth muscle (HJCSM) cells. The aim of this study was to determine the molecular identity of the pore-forming alpha-subunit of the HJCSM Na+ channel. Degenerate primers identified a cDNA fragment of 1.5 kb with 99% nucleotide homology with human(More)
Normal gastrointestinal (GI) motility is required to mix digestive enzymes and food and to move content along the GI tract. Underlying the complex motor patterns of the gut are electrical events that reflect ion flux across cell membranes. Smooth muscle electrical activity is directly influenced by GI interstitial cells of Cajal, whose rhythmic oscillations(More)
A mechanosensitive Na(+) current carried by Na(v)1.5 is present in human intestinal circular smooth muscle and contributes to regulation of intestinal motor function. Expression of this channel in different species is unknown. Our aim was to determine if Na(+) currents and message for the alpha subunit of the Na(+) channel (SCN5A) are found in circular(More)
The gaseous molecule hydrogen sulfide (H(2)S) has been proposed as an endogenous signal molecule and neuromodulator in mammals. Using a newly developed method, we report here for the first time the ability of intact and living brain and colonic tissue in the mouse to generate and release H(2)S. This production occurs through the activity of two enzymes,(More)