Calcium ion channels in myometrium: molecular basis for forceful contractility

Abstract

The entry of calcium ion (Ca²⁺) through voltage-dependent Ca²⁺ channels (VDCCs) is responsible for the excitation-contraction coupling in uterine smooth muscle. VDCCs are opened in response to depolarization of the plasma membrane as action potentials propagated over the surface of muscle cells. This leads to a rapid influx of Ca²⁺, activation of myosin light-chain kinase, and initiation of muscle contraction. Since the contraction of myometrium is dependent upon action potentials, VDCCs play a critical role in the regulation of uterine contractility. On the basis of electrophysiological and pharmacological properties of Ca²⁺ channels, six major types of VDCCs have been described. Most knowledge on the structure of VDCCs, especially the L-type VDCC, comes from research on skeletal muscle. It is now accepted that the VDCC protein is constituted of five subunits (α₁, α₂/δ, β, γ), and that the α₁-subunit is the main, pore-forming, and minimum component of the L-type VDCC. There are some electrophysiological studies with respect to measuring the Ca²⁺ current of the myometrial cells. In the rat myometrium, it has been proposed that Ca²⁺ current density of VDCC may increase during gestation, or may be almost unchanged during pregnancy. We investigated the levels of L-type VDCC subunit mRNA in myometrium to determine whether alterations are associated with term or preterm labor. The observed changes indicate that the mRNA levels increase gradually in the late pregnancy to reach peaks prior to term labor, then decrease sharply during labor and post partum. In addition, antiprogesterone and progesterone treatments, which either stimulate preterm labor or inhibit term labor, respectively increased or decreased the subunit mRNA of VDCCs. These results show that alterations of the VDCC subunit gene transcripts are associated with either the term or preterm labor. The increase in the expression of VDCCs during periods of term and preterm labor may facilitate uterine contractility. However, the development of VDCC mRNA transcript may be only one of many changes that occur in the muscle cells in preparation for forceful contractility to facilitate parturition.