The structure-function relationship of the nicotinic acetylcholine receptor (AChR) has been effectively studied by the combination of complementary DNA manipulation and single-channel current analysis. Previous work with chimaeras between the Torpedo californica and bovine AChR delta-subunits has shown that the region comprising the hydrophobic segment M2 and its vicinity contains an important determinant of the rate of ion transport through the AChR channel. It has also been suggested that this region is responsible for the reduction in channel conductance caused by divalent cations and that segment M2 contributes to the binding site of noncompetitive antagonists. To identify those amino acid residues that interact with permeating ions, we have introduced various point mutations into the Torpedo AChR subunit cDNAs to alter the net charge of the charged or glutamine residues around the proposed transmembrane segments. The single-channel conductance properties of these AChR mutants expressed in Xenopus laevis oocytes indicate that three clusters of negatively charged and glutamine residues neighbouring segment M2 of the alpha-, beta-, gamma- and delta-subunits, probably forming three anionic rings, are major determinants of the rate of ion transport.

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Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3-24.3 (median 15.0) years who had been transplanted 1.5-8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m2. Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants.

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Ambulatory blood pressure monitoring (ABPM) has been shown to be more representative of blood pressure (BP) levels than casual BP measurements in adult patients treated by haemodialysis (HD). In this study we compared ABPM using the oscillometric SpaceLabs 90207 monitor with casual BP measurements in 35 paediatric patients [17 treated by peritoneal dialysis (PD) and 18 by HD]. Heart rate and plasma concentrations of atrial natriuretic peptide were also measured. No correlations were found between ABPM and causal BP measurements, except for systolic day-time BP in PD patients (r = 0.63). Seventy percent of PD and 33% of HD patients were regarded as hypertensive when evaluated by ABPM, while casual BP measurements demonstrated hypertension in 47% (P < 0.05) of PD patients and in 44% (NS) of HD patients. One-third of patients were reclassified by ABPM either from normotensive to hypertensive (7/19) or from hypertensive to normotensive (5/16). BP assessed by ABPM was higher in PD than in HD patients. The physiological decline of BP at night was significant and more pronounced in PD than in HD patients. In HD patients day-time BP did not differ between the 1st and the 2nd interdialytic day, but increased in the night hours before the following dialysis session. A positive correlation was found between day-time BP and pre-dialysis plasma atrial natriuretic peptide in both treatment groups. In conclusion this study demonstrates that casual BP recordings are not representative of average BP in dialysed paediatric patients. ABPM is useful in the diagnosis and treatment of hypertension in children with end-stage renal disease.

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