Ion channels in the plasma membrane of vascular muscle cells that form the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. Current evidence indicates that vascular smooth muscle cells express at least 4 different types of K(+) channels, 1 to 2 types of voltage-gated Ca(2+) channels, >/=2 types of Cl(-) channels, store-operated Ca(+) (SOC) channels, and stretch-activated cation (SAC) channels in their plasma membranes, all of which may be involved in the regulation of vascular tone. Calcium influx through voltage-gated Ca(2+), SOC, and SAC channels provides a major source of activator Ca(2+) used by resistance arteries and arterioles. In addition, K(+) and Cl(-) channels and the Ca(2+) channels mentioned previously all are involved in the determination of the membrane potential of these cells. Membrane potential is a key variable that not only regulates Ca(+2) influx through voltage-gated Ca(2+) channels, but also influences release of Ca(2+) from internal stores and Ca(2+)- sensitivity of the contractile apparatus. By controlling Ca(2+) delivery and membrane potential, ion channels are involved in all aspects of the generation and regulation of vascular tone.