Figure 8.

Vascular K_Ca3.1 channels and their function in proliferating VSM cells. Panel A shows a schematic of an α-subunit demonstrating the typical six-membrane spanning domain structure of K_Ca3.1 channels. Calcium sensitivity is conferred by the Ca²⁺-binding protein, calmodulin, that binds to the channel’s C-terminus. Panel B shows a schematic of the role played by K_Ca3.1 channels in proliferating VSM cells. In proliferating cells, store-operated Ca²⁺ channels, composed of Orai proteins and the Ca²⁺ -sensing protein, STIM, are up-regulated, as are IP₃R receptors. Increases in intracellular Ca²⁺ produced by increased activity of Orai/STIM and IP₃R, activates K_Ca3.1 channels, leading membrane hyperpolarization. This hyperpolarization increases the electrochemical (EC) gradient (grad) for Ca²⁺ diffusion into the cells, augmenting Ca²⁺ influx through Orai/STIM and other non-voltage-gated Ca²⁺ channels in proliferating cells, leading to an increase in intracellular Ca²⁺. This is a positive-feedback system, in contrast to the negative-feedback system that is found in contractile VSM cells (see Figure 3B).