Plasmalemmal Ca²⁺ Signaling in Arterial Smooth Muscle: It's Elementary!

Uniquely among the major intracellular second messengers, calcium is an element; an obvious statement, but one with profound consequences for its signaling functions. Being an element, cells cannot synthesize or degrade calcium, they can only actively move it from one place to another, allow it to move passively down concentration gradients, and let it bind to things. The active moving is done by pumps and transporters that establish enormous (>10,000-fold) concentration gradients of Ca²⁺ ions between the very low basal free [Ca²⁺] in the cytosol (∼50–100 nM) and the much higher concentrations in the extracellular fluid and reservoirs sequestered in intracellular organelles, principally the ER or SR and mitochondria. Opening of Ca²⁺-permeable channels in the plasma or intracellular membranes can then evoke large and extremely rapid increases in local cytosolic [Ca²⁺] as Ca²⁺ ions flow passively down...