Ionic mechanisms and Ca2+ handling in airway smooth muscle

Asthma is a disease characterised by reversible contraction of airway smooth muscle. Many signalling pathways are now known to underlie that contraction, almost all of which revolve around Ca2+ handling. Ca2+ homeostasis in turn is governed by a wide variety of ionic mechanisms, which are still poorly understood. The present review will briefly summarise those mechanisms that have been recognised for decades, but will then devote considerable attention to several novel ionic signalling mechanisms such as capacitative Ca2+ entry, the reverse mode of the Na+/Ca2+ exchanger, the role of CI- channels in the release of internal Ca2+ and that of ryanodine receptors in the refilling of the sarcoplasmic reticulum, as well as the regulation of the monomeric G-protein Rho by ionic mechanisms. Lastly, evidence will be provided that Ca2+- dependent contraction may be driven by spatial and temporal heterogeneities in the intracellular Ca2+ concentration (i.e. Ca2+ waves/oscillations) rather than by an increase in the global steady state intracellular Ca2+ concentration.