AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 207-L213, Copyright © 1995 by American Physiological Society
Role of intracellular pH in relaxation of porcine tracheal smooth muscle by respiratory gases
T. L. Croxton, B. Lande and C. A. Hirshman
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Hypercapnia and hypoxia both relax airway smooth muscle, but the mechanisms
responsible are poorly understood. Because hypercapnia and hypoxia can each
decrease intracellular pH (pHi) and acidosis can inhibit Ca2+ channels, we
hypothesized that decreased pHi mediates relaxation of trachealis muscle by
each of these respiratory gases. To examine the relationship between pHi
and tone, we measured isometric tension, bath pH, and fluorescence
intensity (540 nm) in porcine tracheal smooth muscle strips loaded with
2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and excited alternately
with 440- and 500-nm light. Strips equilibrated in Krebs-Henseleit solution
bubbled with 95% O2-5% CO2 were contracted with carbachol and then relaxed
with either 95% N2-5% CO2 or 93% O2-7% CO2. The ratio of fluorescence
intensity at 500 nm to 440 nm was calibrated vs. pHi with use of nigericin.
Baseline pHi was 7.19 +/- 0.03 (n = 13). Hypoxia decreased active tension
by approximately 60% but did not change pHi. Hypercapnia induced decreases
in tension that were associated with substantial decreases in pHi. Thus,
decreased pHi does not mediate hypoxic relaxation, but the relaxation
during physiologically relevant increases in CO2 concentration is
associated with significant cellular acidification.
