Regulation Of Nerve Activity Research Articles

Discrimination between Alpha-Synuclein Protein Variants with a Single Nanometer-Scale Pore.

Alpha-synuclein is one of several key factors in the regulation of nerve activity. It is striking that single- or multiple-point mutations in the 140-amino-acid-long protein can change its structure, which leads to the protein's aggregation and fibril formation (which is associated with several neurodegenerative diseases, e.g., Parkinson's disease). We recently demonstrated that a single nanometer-scale pore can identify proteins based on its ability to discriminate between protease-generated polypeptide fragments. We show here that a variation of this method can readily discriminate between the wild-type alpha synuclein, a known deleterious point mutation of the glutamic acid at position 46 replaced with a lysine (E46K), and post-translational modifications (i.e., tyrosine Y39 nitration and serine 129 phosphorylation).

Exercise training attenuates baroreflex regulation of nerve activity in rabbits.

Baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) during changes in arterial pressure were examined in conscious rabbits before and after 8 wk of treadmill endurance exercise training. Exercise-induced bradycardia (decreased HR at rest and at identical workloads) was used to document a cardiovascular training effect. At 29.4 m/min, 20% grade, posttraining HR was significantly lower than pretraining values (295 +/- 6 beats/min vs. 361 +/- 8 beats/min, P less than 0.05). Rabbits were instrumented with an occluder around the inferior vena cava (IVCO), arterial and venous catheters, and recording electrodes around renal sympathetic nerves. Baroreflex-mediated changes in HR and RSNA to a 25-mmHg decrease and increase in mean arterial pressure (MAP) were obtained by inflating the IVCO or progressive infusion of phenylephrine, respectively. After training, the range (maximum response minus minimum response) of baroreflex control of RSNA and HR was significantly attenuated (209 +/- 12 vs. 413 +/- 14% and 123 +/- 16 vs. 162 +/- 8 beats/min). In addition, the slope of baroreflex control of HR and RSNA was significantly attenuated after training (4.17 +/- 0.35 vs. 8.32 +/- 0.23%/mmHg and 2.57 +/- 0.4 vs. 4.14 +/- 0.4 beats.min-1.mmHg-1). These data demonstrate that endurance exercise training significantly attenuated baroreflex control of HR and RSNA in conscious rabbits.