Basis of rise in intracellular sodium in airway hyperresponsiveness and asthma.
The aim of this study was to investigate the basis of disturbances in sodium transport in asthma and in airway hyperresponsiveness without symptoms of asthma (asymptomatic AHR). We measured the intracellular sodium (Na(i)); activity of Na(+)/K(+)-ATPase in unstimulated cells (resting activity) and in cell homogenate under optimal conditions (maximal activity); and sodium influx, in mixed leukocytes of 15 normal subjects, 12 subjects with asymptomatic AHR, and 26 asthmatics with or without active symptoms. Resting Na(+)/K(+)-ATPase activity was the same as sodium influx, consistent with homeostasis. Compared with normal subjects, those with asymptomatic AHR or asthma with controlled symptoms had a twofold increase in sodium influx and Na(i). Symptomatic asthmatics also had a twofold increase in sodium influx but a fourfold elevation of Na(i). Maximal Na(+)/K(+)-ATPase activity was reduced by half in symptomatic asthmatics compared with normal subjects. The reduction of maximal Na(+)/K(+)-ATPase activity was associated with a significant decrease in ATP turnover per Na(+)/K(+)-ATPase molecule but not number of Na(+)/K(+)-ATPase molecules per cell. In summary, airway hyperresponsiveness with or without asthma is associated with increased sodium influx and Na in leukocytes. Resting activity of Na(+)/K(+)-ATPase is also increased as a compensatory response to the increased sodium influx, but it is achieved at the expense of higher Na(i). Symptomatic asthma is additionally associated with reduction in maximal activity of Na(+)/K(+)-ATPase, resulting in reduced capacity to handle the increase in sodium influx and consequent severe elevations in Na(i).
Agrawal
Anurag
A
Department of Cardio-respiratory Physiology, Vallabhbhai Patel Chest Institute, University of Delhi, India. aaprawal@bcm.tmc.edu
Agrawal
Krishna P
KP
Ram
Arjun
A
Sondhi
Anita
A
Chhabra
Sunil K
SK
Gangal
Sharad V
SV
Mehta
Dolly
D
D001249:Asthma / Q000097:blood* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000097:blood* / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood*
D000254:Sodium-Potassium-Exchanging ATPase