Activation of Vasopressin Receptor 1A by Vasopressin Enhances Myometrial Smooth Muscle Cell Excitability by Inhibiting the Potassium Channel SLO2.1

AVP enhances excitability in myometrial smooth muscle cells by inhibiting potassium currents, which may influence uterine contraction dynamics.

Summary and findings

This study investigates the role of arginine vasopressin (AVP) in enhancing the excitability of myometrial smooth muscle cells (MSMCs) through the activation of vasopressin receptor 1A (AVPR1A). The research demonstrates that AVP inhibits SLO2.1-mediated potassium currents, reducing current amplitude to approximately 60% of control currents. The findings suggest a mechanism by which AVP enhances intracellular Ca²⁺ signaling in myometrial cells.

Abstract

Arginine vasopressin (AVP) increases excitability of myometrial smooth muscle cells (MSMCs) through Gαq-coupled AVP receptors. Although excitability requires membrane depolarization, the mechanisms linking AVP receptor activation to membrane depolarization and Ca²⁺ signaling are incompletely understood. Here, we show that AVPR1 is the predominant AVP receptor in primary MSMCs. In Xenopus oocytes, AVP signals through AVPR1 to inhibit SLO2.1-mediated potassium currents, reducing current amplitude to approximately 60% of control currents. Consistent with suppression of a hyperpolarizing conductance, AVP depolarized a myometrial cell line (hTERT-HM) and increased intracellular Ca²⁺ signaling. Analysis of Ca²⁺ dynamics revealed that the initial Ca²⁺ peak was largely preserved under conditions limiting extracellular Ca²⁺ entry, consistent with intracellular store release. Conversely, the oscillatory phase depended on extracellular Ca²⁺ influx and was reduced by SLO2.1 knockdown. Together, these findings support a model in which AVP preferentially signals through AVPR1A to inhibit SLO2.1, depolarize myometrial cells, enhance VDCC-dependent Ca²⁺ entry, and promote excitability, enhancing conditions for uterine contraction.

Limitations

Not reported in abstract.

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