TREK-1 currents in smooth muscle cells from pregnant human myometrium. Academic Article uri icon

start page

  • C632

end page

  • C642

abstract

  • The mechanisms governing maintenance of quiescence during pregnancy remain largely unknown. The current study characterizes a stretch-activated, tetraethylammonium-insensitive K(+) current in smooth muscle cells isolated from pregnant human myometrium. This study hypothesizes that these K(+) currents can be attributed to TREK-1 and that upregulation of this channel during pregnancy assists with the maintenance of a negative cell membrane potential, conceivably contributing to uterine quiescence until full term. The results of this study demonstrate that, in pregnant human myometrial cells, outward currents at 80 mV increased from 4.8 ± 1.5 to 19.4 ± 7.5 pA/pF and from 3.0 ± 0.8 to 11.8 ± 2.7 pA/pF with application of arachidonic acid (AA) and NaHCO3, respectively, causing intracellular acidification. Similarly, outward currents were inhibited following application of 10 μM fluphenazine by 51.2 ± 9.8% after activation by AA and by 73.9 ± 4.2% after activation by NaHCO3. In human embryonic kidney (HEK-293) cells stably expressing TREK-1, outward currents at 80 mV increased from 91.0 ± 23.8 to 247.5 ± 73.3 pA/pF and from 34.8 ± 8.9 to 218.6 ± 45.0 pA/pF with application of AA and NaHCO3, respectively. Correspondingly, outward currents were inhibited 89.5 ± 2.3% by 10 μM fluphenazine following activation by AA and by 91.6 ± 3.4% following activation by NaHCO3. Moreover, currents in human myometrial cells were activated by stretch and were reduced by transfection with small interfering RNA or extracellular acidification. Understanding gestational regulation of expression and gating of TREK-1 channels could be important in determining appropriate maintenance of uterine quiescence during pregnancy.

date/time value

  • 2013

Digital Object Identifier (DOI)

  • 10.1152/ajpcell.00324.2012

PubMed Identifier

  • 23804201

volume

  • 305

number

  • 6

keywords

  • Adult
  • Cell Line
  • Female
  • HEK293 Cells
  • Humans
  • Membrane Potentials
  • Muscle Cells
  • Myocytes, Smooth Muscle
  • Myometrium
  • Potassium
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Pregnancy
  • Tetraethylammonium
  • Up-Regulation
  • Young Adult