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Specific Role of Membrane Progesterone Receptors α and β on Ventilation during Sleep in Female Mice.

We recently showed that deletion of nuclear progesterone receptors disrupts breathing during sleep. Here we tested the hypotheses that deletion of membrane progesterone receptors (mPR) α and β in the medulla‐brain stem regions decreases ventilation and increases breathing instabilities during sleep. Female mice were chronically instrumented and small interfering RNA (siRNA) against mPRαor mPRβ (or a control solution) were infused in the fourth ventricle for 2 weeks. Ventilation (Ve) and CO2 production (VCO2) were continuously recorded (whole body plethysmography) during 4 h (9:00‐13:00) in normoxia. Respiratory frequency, tidal volume, minute ventilation and the frequency of spontaneous and post‐sigh apneas were determined during sleep, defined as periods of stable breathing pattern lasting at least 10 minutes. Compared to control, deletion of mPRα decreased Ve and Ve/VCO2 during sleep, but did not affect apnea or sigh frequency. The deletion of mPRβ had no effect on Ve but decreased VCO2, increased Ve/VCO2 and increased the frequency of spontaneous and post‐sigh apneas. Specific deletions of mPRα and mPRβ have been verified by immunohistochemistry on serial brainstem slices. Our results show that mPRα and β play specific role on respiratory control during sleep, and suggest that these receptors mediate some of the respiratory effects of progesterone. Founded by CIHR (MOP‐102715).