VOLTAGE-DEPENDENT CA2-MUSCLE CELLS( CHANNELS IN ARTERIAL SMOOTH)

The past years have seen some significant advances in our understandin g of the functional and molecular properties of voltage-dependent Ca2 channels in arterial smooth muscle. Molecular cloning and expression studies together with experiments on native voltage-dependent Ca2+ cha nnels revealed that these channels are built upon a molecular structur e with properties appropriate to function as the main source for Ca2entry into arterial smooth muscle cells. This Ca2+ entry regulates int racellular free Ca2+, and thereby arterial tone. We summarize several avenues of recent research that should provide significant insights in to the functioning of voltage-dependent Ca2+ channels under conditions that occur in arterial smooth muscle. These experiments have identifi ed important features of voltage-dependent Ca2+ channels, including th e steep steady-state voltage-dependence of the channel open probabilit y at steady physiological membrane potentials between -60 and -30 mV, and a relatively high permeation rate at physiological Ca2+ concentrat ions, being about one million Ca2+ ions/s at -50 mV. This calcium perm eation rate seems to be a feature of the pore-forming Ca2+ channel alp ha(1) subunit, since it was identical for native channels and the expr essed alpha(1) subunit alone. The channel activity is regulated by dih ydropyridines, vasoactive hormones and intracellular signaling pathway s. While the membrane potential of smooth muscle cells primarily regul ates arterial muscle tone through alterations in Ca2+ influx through d ihydropyridine-sensitive voltage-dependent ('L-type') Ca2+ channels, t he role of these channels in the differentiation and proliferation of vascular smooth muscle cells is less clear. We discuss recent findings suggesting that other Ca2+ permeable ion channels might be important for the control of Ca2+ influx in dedifferentiated vascular smooth mus cle cells.