Understanding the control of uterine smooth muscle contractility has important therapeutic implications for the treatment of preterm or dysfunctional labours. In vitro hypoxia (or metabolic inhibition) rapidly reduces contractility in a variety of smooth muscle preparations, including myometrium (Taggart & Wray, 1998), suggesting that hypoxia is likely to influence cellular excitability. TASK (TWIK-related acid-sensitive K+ channel) and TREK (TWIK-related K+ channel) are members of the mammalian two-pore domain K+ channel family that play an essential role in determining resting membrane potential and action potential duration in many electrically excitable cells (Patel & Honore, 2001). Functionally, TASK 1 and 3 are known to be oxygen sensitive, as is the mechano-sensitive member TREK 1, but the expression of these channels in human myometrium is unknown. As human myometrium contracts phasically during labour and is likely to experience periods of hypoxia/reoxygenation, characterisation of these K+ channels may elucidate mechanisms regulating human uterine excitability and contractility. We have therefore examined the mRNA expression of TASK and TREK in human myometrium.
Myometrial tissue was obtained from uterine biopsies (n = 12) of women undergoing hysterectomy or Caesarean section at term (not in labour and in active labour). Biopsies were taken with informed written consent and according to local ethical committees’ regulations. Total RNA was extracted and quantified from each sample using standard techniques. RT-PCR was performed using gene-specific primers for TASK 1 to 5 and TREK 1 and 2 that amplified products of correct sizes (relative to a molecular ladder) when validated with control tissues (commercial human brain or placental total RNA; Becton Dickinson Bioscience). TASK 1, 4, 5 and TREK 1 mRNA was detected in all myometrial tissues, whereas expression of TASK 2 and 3 was variable. TREK 2 was not detected in human myometrium.
These data demonstrate that mRNA encoding certain TASK and TREK members of the two-pore domain K+ channel family are expressed in human myometrium.
This work was supported by Tommy’s, the baby charity.