Calcium channels expressed in vascular smooth muscle.

Abstract

Regulation of intracellular calcium levels is known to activate signal transduction pathways, leading to well-defined patterns of gene expression. Among the calcium-responsive genes are those involved in the growth and proliferative responses of vascular smooth muscle cells. Cytoplasmic calcium also plays a role in activating a host of cellular functions including smooth muscle contraction and growth factor release. Calcium channels participate in the regulation of cytoplasmic calcium concentration in vascular smooth muscle. Two major classes of calcium channels are expressed in vascular smooth muscle cells: voltage-dependent calcium channels on the plasmalemma and intracellular calcium release channels on the endoplasmic reticulum. The voltage-dependent calcium channel is activated by depolarization of the plasmalemma. This calcium channel belongs to the super gene family that includes the voltage-dependent potassium and sodium channels. These three cation channels share a common transmembrane topography. The major intracellular calcium release channel in vascular smooth muscle is the inositol 1,4,5-trisphosphate receptor (IP3R) on the endoplasmic reticulum. The IP3R is activated by IP3, a second messenger generated at the plasmalemma, which mediates numerous cellular responses including smooth muscle contraction. Also present in smooth muscle cells is the ryanodine receptor (RYR)/calcium release channel of the sarcoplasmic reticulum. The RYR is the major intracellular calcium release channel of striated muscles and is expressed in relatively low levels in vascular smooth muscle. The IP3R and RYR are members of a gene family encoding intracellular calcium release channels with characteristic fourfold symmetric structures.