Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis

Abstract

Background: Adenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM.

Methods: Uterine tissue samples from 22 patients (cases) with histologically confirmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real-time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K + channel (BKCa)-α/β subunits, voltage-gated potassium channel (Kv) 4.2, and Kv4.3. Student's t-test was used to compare the expression.

Results: The BKCa-α/β subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-β subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-α messenger RNA (mRNA) (0.62 ± 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 ± 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-β subunit mRNA or Kv4.2 mRNA.

Conclusions: The BKCa-α mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain.

Figure 1

Immunohistochemistry staining of paraffin-embedded sections. (A-D) Strong BKCa-α expression in smooth muscle cells with adenomyosis or not, ectopic or eutopic glandular epithelial cells and stromal cells (original magnification, ×400). So was the expression of Kv 4.2 (I-L) (original magnification, ×200). Moderate BKCa-β expression in smooth muscle cells of the adenomyotic lesion and the control myometrium (E-H) (original magnification, ×100). Weak Kv4.3 expression in myometrium without adenomyosis, while strong stained immunoreactive smooth muscle cell, ectopic glands, and stromas of adenomyosis (M-P) (original magnification, ×200).

Figure 2

Human endometrial epithelia and stromal areas were laser-microdissected (a → b), and myometrium was left for RNA extraction (original magnification ×100).

Figure 3

The relative mRNA expression in adenomyosis (AM) and the control group. The expression of BKCa-alpha (a) was significantly increased in myometrium of AM compared to the control group (P < 0.05), so was Kv4.3 (d). The relative expression of mRNA for BKCa-beta (b) and Kv4.2 (c) showed no statistically significant difference.