DYNAMICS OF ION CHANNEL EXPRESSION IN PREGNANT RAT MYOMETRIUM : ANALYSIS MOLECULAR PHYSIOLOGICAL

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Yamagata University
• Principal Investigator: TEZUKA Naohiro YAMAGATA UNIV., SCHOOL OF MED., ASSISTANT PROF., 医学部, 講師 (60261690)
• Co-Investigator(Kenkyū-buntansha): IGARASHI Hideki YAMAGATA UNIV., SCHOOL OF MED., LECTURER, 医学部, 助手 (80333970) ; TAKAHASHI Kazuhiro YAMAGATA UNIV., SCHOOL OF MED., LECTURER, 医学部, 助手 (20292427) ; KURACHI Hirohisa YAMAGATA UNIV., SCHOOL OF MED., PROFESSOR, 医学部, 教授 (40153366)
• Project Period (FY): 2002 – 2004
• Keywords: Myometrium / Ion channel / Molecular physiology

Research Abstract

Calcium ion entry through voltage-dependent clcium ion channels (VDCCs) is responsible for excitation-contraction coupling in uterine smooth muscle. VDCCs are opened in response to depolarization of the plasma membrane as action potentials propagate over the surface of the muscle cell. This leads to a rapid influx of clcium ion, activation of myosin light-chain kinase, and initiation of muscle contraction. Since contraction of the 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 clcium ion channels, six major types of VDCCs have been descrided. Most information about VDCC structure especially the L-type VDCC comes from research on skeletal muscle. It is now accepted that the VDCC protein is constituted of five subunits, and that the α1 sbunit is the main, pore-forming, and minimum component of the L-type VDCC. There are some electrophysiological s tudies with respect to measuring the clcium ion current of the myometrial cells. In the rat myometrium, it has been proposed that clcium ion 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 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 term or preterm labor. The increase in 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.