Ion channels in uterine smooth muscle cells to regulate ­contractions during term and preterm delivery: Role of non-selective cation channels and gap junctions

Keywords:

uterine smooth muscle cells, ion channel, non-selective cation channel, ATP receptor, gap junction, magnesium

H. Miyoshi1,2, S. Urabe3, Y. Kudo2
1Department of Obstetrics and Gynecology, Higashihiroshima Medical Center, 513 Jike, Saijyo-chou, Higashihiroshima, Hiroshima 739-0041, Japan.
2Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

3Department of Obstetrics and Gynecology, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda, Minami-ku, Hiroshima 734-8530, Japan.

Correspondence at: miyoshi_hiroshi@hiro-hosp.jp

Abstract

Uterine contractions are generated by calcium (Ca2+) influx into myometrial cells which is regulated by the membrane potential of myometrial cells. Non-selective cation channels (NSCCs) associated with membrane potential were studied in rat myometrial cells using the patch-clamp method and molecular biological techniques. Two types of NSCC current in myometrial cells were detected. One is lanthanum (La) sensitive NSCC current and the other is adenosine triphosphate (ATP) induced current. Purinergic P2X7 receptor was determined to be the functional channel for ATP induced currents. These NSCCs are suggested to be mechanisms to generate spontaneous ­depolarizations, leading to rhythmical uterine contractions. Blocking of these NSCCs by magnesium ions (Mg2+) may be one of the mechanisms for inhibiting uterine contractions in tocolysis. Cell-to-cell couplings through gap junction (GJ) channels increase at the end of pregnancy. We used the double patch-clamp technique on myometrial paired cells and characterized GJ currents. Most properties were comparable to those of connexin 43, indicating that connexin 43 is the main component of myometrial GJ. Junctional conductance between myometrial cells was enhanced sixfold in preterm delivering compared with preterm non-delivering rats. This enhancement is caused by an increase in the number of GJ channels. Finally, the expression of P2X receptors was examined in the ­myometrium, and P2X4 and P2X7 were expressed most strongly. The expression levels of these receptors increases in the late stages of pregnancy. Lipopolysaccharide, an endotoxin, significantly increased these levels, showing that inflammation is associated with preterm delivery.