Estrogen Regulates the Expression of Small-Conductance Ca²⁺-Activated K⁺ Channels in Colonic Smooth Muscle Cells

Abstract

Aim: This study aimed to determine the effects of small-conductance Ca²⁺-activated K⁺ (SK) channels in colonic relaxation and the regulation of SK channels by estrogen. Methods: The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17β-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERβ agonist). SK3 mRNA and protein expression levels were detected. Results: The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3. Conclusion: These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.

Effect of Gonadal Hormones on Colonic Contractile Activity in Albino Rats

“…This finding was supported by Hogan et al, who found that EST decreased human colonic smooth muscle contractility [18]. Our results were also in agreement with Tang et al, [29] who showed similar results in colonic circular muscle of rats. Also, EST has been demonstrated to inhibit smooth muscle contractility in other tissues such as the gall bladder [30] esophagus [31] and detrusor [32,33].…”

In vitro spontaneous contractile activity of colonic smooth muscle in naive Lewis rats: Acute effect of gonadal hormones

“…In an in vitro study performed by Hogan et al EST has been shown to decrease human colonic smooth muscle contractility, 33 while another study showed similar results in colonic circular muscle of rats. 45 These findings are consistent with the results obtained in our in vitro study with rats where EST inhibited the SCCA. However, EST has been demonstrated to inhibit smooth muscle contractility in other tissues, such as the gall bladder, 46 esophagus, 47 detrusor, 48,49 aorta, 50 coronary arteries 51 and the carotid artery.…”

“…The inhibitory effect of the acute administration of female gonadal hormones on gastrointestinal smooth muscle contractility that contrasts with physiological chronic action has been investigated in several previous studies. In an in vitro study performed by Hogan et al EST has been shown to decrease human colonic smooth muscle contractility, while another study showed similar results in colonic circular muscle of rats . These findings are consistent with the results obtained in our in vitro study with rats where EST inhibited the SCCA.…”

Potassium Channels in the Vascular Diseases

“…SK and IK channels are two distinct types of voltage-independent K Ca channels; these channels exhibit a close association between their calcium sensitivity and calmodulin [42]. In contrast to intestinal smooth muscle, little evidence is available suggesting a functional role for SK channels in vascular smooth muscle cells, although an unidentified apamin (a specific blocker of SK channel channels)-sensitive and voltage-dependent conductance has been reported [43]. In healthy and freshly isolated vascular smooth muscle cells, IK channels are expressed at very low levels.…”