Cellular Na(+) handling mechanisms involved in airway smooth muscle contraction (Review)

A decrease in bronchial diameter is designated as bronchoconstriction (BC) and impedes the flow of air through the airway. Asthma is characterized by inflammation of the airways, reversible BC and nonspecific hyperreactivity. These last two symptoms are dependent on airway smooth muscle. Stimuli that trigger contraction can be characterized as chemical (neurotransmitters, cytokines and terpenoids) and physical (volume inspired, air pressure). Both stimuli activate signaling pathways by acting on membrane proteins and facilitating the passage of ions through the membrane, generating a voltage change and a subsequent depolarization. Na(+) plays an important role in preserving the resting membrane potential; this ion is extracted from the cells by the Na(+)/K(+) ATPase (NKA) or introduced into the cytoplasm by the Na(+)/Ca(2+) exchanger (NCX). During depolarization, Na(+) appears to accumulate in specific regions beneath the plasma membrane, generating local concentration gradients which determine the handling of Ca(2+). At rest, the smooth muscle has a basal tone that is preserved by the continuous adjustment of intracytoplasmic concentrations of Ca(2+) and Na(+). At homeostasis, the Na(+) concentration is primarily dependent on three structures: the NKA, the NCX and non-specific cation channels (NSCC). These three structures, their functions and the available evidence of the probable role of Na(+) in asthma are described in the present review.