Ca2+ handling in airway smooth muscle: A historical perspective and novel developments

In airway smooth muscle, the cytosolic concentration of Ca²⁺ (|Ca²⁺]i) is very tightly controlled by an elaborate array of mechanisms. The latter include multiple entry pathways from the extracellular space, a pump on the membrane which extrudes Ca²⁺ out of the cell as well as an internal pump which sequesters Ca²⁺ into an intracellular pool, and at least two types of release sites by which the sequestered Ca²⁺ can be released back into cytosol; all of these are under tight regulation by second messenger signalling pathways. Our understanding of the relationship between Ca²⁺ handling and contraction ("excitation-contraction coupling") has progressed: from a mechanism in which activation of voltage-dependent Ca²⁺ channels plays a central role (as in skeletal muscle), to a mechanism in which localized signalling event triggers a massive release of internal Ca²⁺ (as in cardiac muscle), to a more complicated model in which the internal Ca ²⁺ pool divides the cytosol into two physiologically distinct spaces in which |Ca²⁺|i is regulated independently (as in vascular smooth muscle).