Distribution, expression and functional effects of small conductance Ca-activated potassium (SK) channels in rat myometrium

Cell Calcium. 2010 Jan;47(1):47-54. doi: 10.1016/j.ceca.2009.11.004. Epub 2009 Dec 6.

Abstract

Calcium-activated potassium channels are important in a variety of smooth muscles, contributing to excitability and contractility. In the myometrium previous work has focussed on the large conductance channels (BK), and the role of small conductance channels (SK) has received scant attention, despite the finding that over-expression of an SK channel isoform (SK3) results in uterine dysfunction and delayed parturition. This study therefore characterises the expression of the three SK channel isoforms (SK1-3) in rat myometrium throughout pregnancy and investigates their effect on cytosolic [Ca] and force and compares this with that of BK channels. Consistent expression of all SK isoform transcripts and clear immunostaining of SK1-3 was found. Inhibition of SK1-3 channels (apamin, scyllatoxin) significantly inhibited outward current, caused membrane depolarisation and elicited action potentials in previously quiescent cells. Apamin or scyllatoxin increased the amplitude of [Ca] and force in spontaneously contracting myometrial strips throughout gestation. The functional effect of SK inhibition was larger than that of BK channel inhibition. Thus we show for the first time that SK1-3 channels are expressed and translated throughout pregnancy and contribute to outward current, regulate membrane potential and hence Ca signals in pregnant rat myometrium. They contribute more to quiescence that BK channels.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Apamin / pharmacology
  • Calcium / metabolism
  • Cells, Cultured
  • Excitation Contraction Coupling / drug effects
  • Excitation Contraction Coupling / physiology*
  • Female
  • Gene Expression Regulation
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Myometrium / drug effects
  • Myometrium / physiology*
  • Organ Culture Techniques
  • Potassium Channel Blockers / pharmacology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Scorpion Venoms / pharmacology
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Uterine Contraction / drug effects
  • Uterine Contraction / physiology*

Substances

  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channel Blockers
  • Scorpion Venoms
  • Small-Conductance Calcium-Activated Potassium Channels
  • leiurotoxin I
  • Apamin
  • Calcium