Cellular mechanisms regulating [Ca2+]i smooth muscle.

The preceding chapters establish the primary role of Ca2+ in the activation of smooth muscle contractile proteins. In this chapter we discuss the Ca2+ transport mechanisms that determine the intracellular Ca2+ concentration ([Ca2+U and thus regulate smooth muscle contraction. Two integrated membrane systems are involved in the control of smooth muscle [Ca2+l;: (a) the plasmalemma, which is under the control of the membrane potential (Em) and agonists such as neurotransmitters hormones and autocoids, and (b) the sarcoplasmic reticulum, which is under the control of second messengers. Both membranes form a barrier to an approximately IO,OOO-foid concentration gradient; thus, an increase in permeability to Ca2+ leads to an increase in [Ca2+l;, while active ATP-fueled Ca2+ pumping and possibly Na+ -Ca2+ exchange leads to a decrease in [Ca2+l;. Plasmalemmal Ca2+ permeability is regulated by the voltage gated Ca2+ channels (VGCs) and by chemical gating of receptor operated channels (ROCs) (11, 83). In some cases, agonists also inhibit the Ca2+ extrusion pump (23). The mem­ brane potential is determined by ionic concentration gradients and per­ meabilities according to the Goldman equation and is regulated close to the K+ equilibrium potential by the opening or closing of K+ channels (11).